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<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="eLUa0l2u5fMN3l1tMydmpw7TMDul4hSIvyEfDbvQFQzhXM7jpRQoTEDxkHcxXSq2">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="eLUa0l2u5fMN3l1tMydmpw7TMDul4hSIvyEfDbvQFQzhXM7jpRQoTEDxkHcxXSq2">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="eLUa0l2u5fMN3l1tMydmpw7TMDul4hSIvyEfDbvQFQzhXM7jpRQoTEDxkHcxXSq2">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="eLUa0l2u5fMN3l1tMydmpw7TMDul4hSIvyEfDbvQFQzhXM7jpRQoTEDxkHcxXSq2">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="eLUa0l2u5fMN3l1tMydmpw7TMDul4hSIvyEfDbvQFQzhXM7jpRQoTEDxkHcxXSq2">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="21646512">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://www.pnas.org/doi/10.1073/pnas.1016531108?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub 0pubmed"
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ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=4487&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=21646512&amp;db=pubmed&amp;nlmid=7505876"
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Atypon
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/21646512/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=21646512&amp;db=pubmed&amp;nlmid=7505876"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="21646512"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/21646512/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/21646512/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="21646512" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F21646512%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="eLUa0l2u5fMN3l1tMydmpw7TMDul4hSIvyEfDbvQFQzhXM7jpRQoTEDxkHcxXSq2"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
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<p>
Bardet-Biedl syndrome (BBS) is a pleiotropic, heterogeneous human disease whose etiology lies primarily in dysfunctional basal bodies and/or cilia. Both BBS patients and several BBS mouse models exhibit impaired olfactory function. To explore the nature of olfactory defects in BBS, a genetic ablation of the mouse Bbs8 gene that incorporates a fluorescent reporter protein was created. The endogenous BBS8 protein and reporter are particularly abundant in olfactory sensory neurons (OSNs), and specific BBS8 antibodies reveal staining in the dendritic knob in a shell-like structure that surrounds the basal bodies. Bbs8-null mice have reduced olfactory responses to a number of odorants, and immunohistochemical analyses reveal a near-complete loss of cilia from OSNs and mislocalization of proteins normally enriched in cilia. To visualize altered protein localization in OSNs, we generated a SLP3(eGFP) knock-in mouse and imaged the apical epithelium, including dendritic knobs and proximal cilia, in ex vivo tissue preparations. Additionally, protein reagents that reflect the characteristic neuronal activity of each OSN revealed altered activity in Bbs8-null cells. In addition to previously known defects at the ciliary border, we also observed aberrant targeting of OSN axons to the olfactory bulb; axons expressing the same receptor display reduced fasciculation and project to multiple targets in the olfactory bulb. We suggest that loss of BBS8 leads to a dramatic and variable reduction in cilia, the essential signaling platform for olfaction, which alters the uniformity of responses in populations of OSNs expressing the same receptor, thereby contributing to the observed axon-targeting defects.
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">The authors declare no conflict of interest.</p>
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<p> Fig. 1. </p>
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<div class="figure-caption-contents"><p> Genetic ablation of the <i> Bbs8… </i> </p></div>
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<p> Fig. 1. </p>
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<div class="figure-caption-contents"><p> Genetic ablation of the <i> Bbs8 </i> gene. ( <i> A </i> ) In situ hybridization reveals… </p></div>
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<div class="figure-caption-contents">Genetic ablation of the <i>Bbs8</i> gene. (<i>A</i>) In situ hybridization reveals <i>Bbs8</i> mRNA enrichment in OE neurons (<i>Left</i>) and absence in the OE of <i>Bbs8<sup>/</sup></i> mice (<i>Right</i>). (<i>B</i>) Immunofluorescence localizes BBS8 protein (green) predominantly to dendritic knobs marked by γ-tubulin (red), a basal body protein. The BBS8 protein signal is absent in <i>Bbs8<sup>/</sup></i> tissue but γ-tubulin staining persists (<i>Right</i>). (<i>C</i>) High-magnification image of OE cryosections at the cilia layer reveals distinct localization within the dendritic knob, as seen in a cross-section (<i>Upper</i>, a higher magnification of <i>B</i>) and in an en face section (<i>Lower</i>). The basal body-associated γ-tubulin staining resides in the core of each knob, and the BBS8 immunofluorescence forms a surrounding shell. (<i>D</i>) Low-power image of an OB cryosection from a <i>Bbs8<sup>+/</sup></i> mouse reveals intense intrinsic fluorescence from the tau:YFP reporter. Signal is seen specifically in OSN axons projecting from the OE through the olfactory nerve layer and terminating in the olfactory glomeruli. [Scale bar: 10 μm (<i>B</i> and <i>C</i>); 500 μm (<i>D</i>).]</div>
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<p> Fig. 2. </p>
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<div class="figure-caption-contents"><i> Bbs8 <sup> / </sup> </i> mice exhibit reduced…</div>
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<div class="figure-caption-contents"><i> Bbs8 <sup> / </sup> </i> mice exhibit reduced responses to odorants. Peak voltage responses in EOG…</div>
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<div class="figure-caption-contents"><i>Bbs8<sup>/</sup></i> mice exhibit reduced responses to odorants. Peak voltage responses in EOG recordings from <i>Bbs8<sup>+/</sup></i> or <i>Bbs8<sup>/</sup></i> OE exposed to odorants at the indicated molar concentrations. Each bar represents the average responses for <i>Bbs8<sup>+/</sup></i> (<i>n</i> = 12 electrodes/4 mice) or <i>Bbs8<sup>/</sup></i> mice (<i>n</i> = 13 electrodes/4 mice) ± SD. (<i>Inset</i>) Representative responses to a pulse of 10<sup>4</sup> M amyl acetate.</div>
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<div class="figure-caption-contents"><p> Structural and protein localization defects… </p></div>
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<div class="figure-caption-contents"><p> Structural and protein localization defects in <i> Bbs8 <sup> / </sup> </i> OE. OE cryosections from <i> Bbs8… </i> </p></div>
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<div class="figure-caption-contents">Structural and protein localization defects in <i>Bbs8<sup>/</sup></i> OE. OE cryosections from <i>Bbs8<sup>+/</sup></i> or <i>Bbs8<sup>/</sup></i> animals were immunostained and imaged by confocal microscopy (<i>A</i>: single plane, <i>B</i> and <i>C</i>: flattened Z-stacks). (<i>A</i>) Cilia abundance, visualized by acetylated tubulin, is dramatically reduced in <i>Bbs8<sup>/</sup></i> mice. (<i>B</i>) The signal transduction proteins ACIII and ORI7 show reduced intensity in the cilia layer and mislocalization within the dendrite in <i>Bbs8<sup>/</sup></i> OE. (<i>C</i>) SLP3 shows reduced signal at the cilia layer and accumulation within the dendrite and apical cell body. (<i>D</i>) SEM of the olfactory epithelium of 37-wk-old littermates. [Scale bar: 10 μm (<i>A</i><i>C</i>); 2 μm (<i>D</i>).]</div>
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<div class="figure-caption-contents"><p> Localization of endogenous SLP3 in… </p></div>
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<div class="figure-caption-contents"><p> Localization of endogenous SLP3 in OSNs. SLP3:eGFP localizes to the dendritic knob and… </p></div>
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<div class="figure-caption-contents">Localization of endogenous SLP3 in OSNs. SLP3:eGFP localizes to the dendritic knob and proximal regions of cilia in low-power (<i>Left</i>) and high-power (<i>Right</i>) confocal images of the apical surface of unfixed whole-mount OE at the level of the dendritic knobs. The membrane that forms the surface of the dendritic knob and the proximal portions of cilia appear as a “starburst” pattern when visualizing the intrinsic SLP3:eGFP signal. (Scale bar: 20 μm.)</div>
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<div class="figure-caption-contents"><p> SLP3:eGFP expression and localization is… </p></div>
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<p> Fig. 5. </p>
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<div class="figure-caption-contents"><p> SLP3:eGFP expression and localization is altered in <i> Bbs8 <sup> / </sup> </i> OSNs. The fluorescent signals… </p></div>
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<div class="figure-caption-contents">SLP3:eGFP expression and localization is altered in <i>Bbs8<sup>/</sup></i> OSNs. The fluorescent signals from the <i>Bbs8</i> promoter-driven tau:YFP reporter (red) and SLP3:eGFP (green) were separated by linear unmixing. (<i>A</i>) In en face images of the cilia layer, SLP3:eGFP is expressed in most, if not all, dendritic knobs of <i>Bbs8<sup>+/</sup></i> mice, but is visible in only a few scattered cells of the <i>Bbs8<sup>/</sup></i> OE. (<i>B</i>) At high magnification, the altered localization of SLP3eGFP in <i>Bbs8<sup>/</sup></i> OSNs is apparent. Specifically, in <i>Bbs8<sup>+/</sup></i> OE, SLP3:eGFP is restricted to the dendritic knob and proximal cilia (<i>A</i> and <i>B</i>, <i>Left</i>). In <i>Bbs8<sup>/</sup></i> OE (<i>A</i> and <i>B</i>, <i>Right</i>), it is distributed along the length of longer ciliary processes, which also display unusual swellings throughout the extent of the cilia. (Scale bar: 20 μm.)</div>
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<p> Fig. 6. </p>
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<div class="figure-caption-contents"><i> Bbs8 <sup> / </sup> </i> OSNs display increased…</div>
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<p> Fig. 6. </p>
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<div class="figure-caption-contents"><i> Bbs8 <sup> / </sup> </i> OSNs display increased variability in S100A5 protein expression. Sections of OE…</div>
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<div class="figure-caption-contents"><i>Bbs8<sup>/</sup></i> OSNs display increased variability in S100A5 protein expression. Sections of OE from <i>Bbs8</i>/M72<sup>TL</sup> mice were stained for lacZ and S100A5 to determine the expression level of S100A5 in individual OSNs from a defined OR population. Images show a lacZ-positive <i>Bbs8<sup>+/</sup></i> OSN with relatively low S100A5 levels (<i>Upper</i> panels) and a <i>Bbs8<sup>/</sup></i> OSN with high S100A5 levels (<i>Lower</i> panels). (<i>Graph</i>) The mean S100A5 pixel fluorescence intensity, normalized to lacZ intensity, was determined within each cell body for 30 M72-expressing OSNs (<i>n</i> = 3 animals) for each genotype. (Scale bar: 5 μm.)</div>
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<div class="figure-caption-contents"><p> OSN axon targeting is perturbed… </p></div>
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<p> Fig. 7. </p>
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<div class="figure-caption-contents"><p> OSN axon targeting is perturbed in <i> Bbs8 <sup> / </sup> </i> mice. The OR reporter line… </p></div>
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<div class="figure-caption-contents">OSN axon targeting is perturbed in <i>Bbs8<sup>/</sup></i> mice. The OR reporter line M72<sup>TL</sup> was crossed into a <i>Bbs8</i> mutant background and axon targeting was analyzed by whole-mount X-Gal staining of PD15 mice. In dorsal views, axons project from the OE (on the bottom) to their targets in the OB. In <i>Bbs8<sup>+/+</sup></i> mice, M72-tau:lacZexpressing axons converge to one dorsal glomerulus in each bulb. In the OB of <i>Bbs8</i>-deficient mice, multiple glomeruli are innervated and individual fibers wander on the surface of the bulb.</div>
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<div class="figure-caption-contents"><p> Model for olfactory defects seen… </p></div>
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<p> Fig. 8. </p>
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<div class="figure-caption-contents"><p> Model for olfactory defects seen in <i> Bbs8 <sup> / </sup> </i> mice. ( <i> Upper </i> ) In… </p></div>
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<div class="figure-caption-contents">Model for olfactory defects seen in <i>Bbs8<sup>/</sup></i> mice. (<i>Upper</i>) In WT mice, the transduction proteins are restricted to a uniform complement of long cilia, resulting in consistent activity levels among cells expressing the same OR. Activity levels are correlated with abundance of axon guidance and cell adhesion molecules (colored rings). (<i>Lower</i>) <i>Bbs8<sup>/</sup></i> OSNs display variability in cilia number and morphology. This leads to increased heterogeneity in neuronal activity and corresponding variability in S100A5 levels among OSNs expressing the same OR, depicted as differently shaded OSNs. The greater variation in abundance and diversity of axon guidance and cell adhesion molecules on the OSN axons would affect the fidelity of targeting.</div>
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