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. 2002 Jun;50(6):790-6.
doi: 10.1136/gut.50.6.790.

Novel human and mouse genes encoding an acid phosphatase family member and its downregulation in W/W(V) mouse jejunum

I Takayama  1 , Y Daigo, S M Ward, K M Sanders, R L Walker, B Horowitz, T Yamanaka, M A Fujino
Affiliations

Novel human and mouse genes encoding an acid phosphatase family member and its downregulation in W/W(V) mouse jejunum

I Takayama et al. Gut. 2002 Jun.

Abstract

Background and aims: Interstitial cells of Cajal (ICC) are pacemakers and mediators of motor neurotransmission in gastrointestinal smooth muscles. ICC require cellular signalling via Kit, a receptor tyrosine kinase, for development and maintenance of phenotype. Much of the evidence demonstrating the functions of ICC comes from studies of W/W(V) mice, which have reduced Kit function and reductions in specific populations of ICC. The aim of the present study was to differentially examine gene expression in the small intestines of wild-type and W/W(V) mutant mice.

Methods and results: RNA from the jejunums of wild-type and W/W(V) mutants was analysed using a differential gene display method. Eighteen queries were identified as novel genes that were differentially displayed in wild-type and W/W(V) mice. One candidate gene, encoding a novel acid phosphatase-like protein, was significantly suppressed in fed and starved W/W(V) mice. The full length clone of the murine gene and its human counterpart were designated acid phosphatase-like protein 1 (ACPL1). Human ACPL1 cDNA encodes a protein of 428 amino acids with homology to human prostatic acid phosphatase protein. This gene is located at 1q21. ACPL1 was abundantly expressed in the human small intestine and colon. Gene products were found to be cytoplasmic in transfected COS-7 cells. Reverse transcription-polymerase chain reaction analysis revealed expression of ACPL1 mRNA within single isolated ICCs.

Conclusions: Gene analysis showed that ACPL1 was differentially expressed in the small intestines of normal and W/W(V) mice. ICC within the small intestine expressed mRNA for ACPL1. Specific downregulation of ACPL1 in the jejunums of W/W(V) mice and high expression in human intestinal tissue suggest that the ACPL1 gene could be associated with ICC function in mice and humans.

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Figures

Figure 1
Figure 1
(A, B) Comparison of the gross morphology of the gastrointestinal tracts from wild-type and W/WV mutant animals, respectively. Note the distended appearance of the stomach and intestines of W/WV mutants (B). Kit-like immunoreactivity revealed the presence of interstitial cells of Cajal (ICC) at the level of the myenteric plexus (IC-MY) (C; arrows) and ICC at the level of the deep muscular plexus (IC-DMP) (arrowheads) in wild-type animals. In W/WV mutants, only IC-DMP were observed (D; arrowheads). The absence of IC-MY in W/WV mutants was also confirmed by electron microscopy (E, F). IC-MY (arrow) and IC-DMP (arrowheads) were readily observed within the circular muscle layer (cm) of jejunums from wild-type animals (E) but only IC-DMP were observed within the cm of W/WV muscles. IC-MY were never observed at the level of the myenteric plexus (*) of W/WV mutant animals. Scale bars are as indicated on each panel.
Figure 2
Figure 2
Expression of acid phosphatase-like protein 1 (ACPL1) using reverse transcription-polymerase chain reaction analysis in jejunum tissues from two wild-type and two W/WV mutant mice maintained under fed and starved conditions. F and S indicate samples of fed and staved mice, respectively. Glyceraldehyde-3- phosphate dehydrogenase (G3PDH) levels were measured as a control. Expression of the 54M clone was considerably reduced in the jejunums of W/WV mice compared with age matched wild-type mice.
Figure 3
Figure 3
Alignment of the predicted amino acid sequences of the acid phosphatase (ACP) family. Included is human acid phosphatase-like protein 1 (ACPL1), mouse ACPL1, human prostatic acid phosphatase (PAP), and human lysosomal acid phosphatase (ACP2) (GenBank accession Nos AB030038, AB0300039, X53605, and P11117, respectively). Shading indicates homologues residues among ACPL1 (human and mouse) and two known human acid phosphatases. ACPL1 is highly conserved between the two species and is also similar to proteins belonging to the family of acid phosphatases (PAP and ACP2).
Figure 4
Figure 4
Northern blot analysis of acid phosphatase-like protein 1 (ACPL1) in various human tissues including the spleen, thymus, prostate, testis, ovary, small intestine, colon without mucosa, and peripheral blood leucocytes. Each lane contained approximately 2 μg of poly A+ RNA. Molecular sizes are indicated as kbp on the left of the column. Arrow donates the position of ACPL1.
Figure 5
Figure 5
Chromosomal mapping of the acid phosphatase-like protein 1 (ACPL1) gene. Prometaphase chromosomes stained with propidium iodide show twin spot signals (green) on chromosome 1q21 (indicated by arrows) mapping the location of the ACPL1 gene.
Figure 6
Figure 6
Cellular localisation of the acid phosphatase-like protein 1 (ACPL1) in mammalian cells after transfection of COS-7 cells using immunohistochemistry. Cells were labelled with antibodies against ACPL1/c-myc protein and DAPI. ACPL1/c-myc protein was located within the cytoplasm of CPS-7 cells but was not specifically associated with any cellular organelle.
Figure 7
Figure 7
Using reverse transcription-polymerase chain reaction, coexpression of mRNA for acid phosphatase-like protein 1 (ACPL1) and Kit was identified within a single interstitial cell isolated from the jejunum of a wild-type animal by enzymatic dispersion.; IC-DMP, ICC at the level of the deep muscular plexus; IC-MY, interstitial cells of Cajal ICC at the level of the myenteric plexus.
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References

    1. Langton PD, Ward SM, Carl A, et al. Spontaneous electrical activity of interstitial cells of Cajal isolated from canine proximal colon. Proc Natl Acad Sci USA 1989;86:7280–4. - PMC - PubMed
    1. Ward SM, Burns AJ, Torihashi S, et al. Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol (Lond) 1994;480:91–7. - PMC - PubMed
    1. Huizinga JD, Thuneberg L, Kluppel M, et al. W/Kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature (Lond) 1995;373:347–9. - PubMed
    1. Ordog T, Ward SM, Sanders KM. Interstitial cells of Cajal generate electrical slow waves in the murine stomach. J Physiol (Lond) 1999;518:257–69. - PMC - PubMed
    1. Burns AJ, Herbert TM, Ward SM, et al. Interstitial cells of Cajal inhibitory neurotransmission in the stomach. Proc Natl Acad Sci USA 1996;93:12008–13. - PMC - PubMed

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