SMALL INTESTINE

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^1,*, S M Ward², K M Sanders², R L Walker², B Horowitz², T Yamanaka¹, M A Fujino¹

¹ Department of Medicine, Yamanashi Medical University School of Medicine, Yamanashi 409-3898, Japan
² Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA

Correspondence to:
Correspondence to:
Dr I Takayama, Department of Medicine, Yamanashi Medical University School of Medicine, Yamanashi 409-3898, Japan;
ichirot{at}is.icc.u-tokai.ac.jp

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.

Keywords: gastrointestinal motility; interstitial cells of Cajal; pacemaker deficient mice; acid phosphatase family; acid phosphatase-like protein 1; chromosome 1q21 differential gene display method

Abbreviations: ACPL1, acid phosphatase-like protein 1; ACP2, lysosomal acid phosphatase; ESTs, expressed sequence tags; FISH, fluorescence in situ hybridisation; ICC, interstitial cells of Cajal; IC-DMP, ICC at the level of the deep muscular plexus; IC-IM, intramuscular ICC; IC-MY, ICC at the level of the myenteric plexus; PAP, prostatic acid phosphatase; RT-PCR, reverse transcription-polymerase chain reaction

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