Takayama I, Daigo Y, Ward S M, Sanders K M, Walker R L, Horowitz B, Yamanaka T, Fujino M A
Department of Medicine, Yamanashi Medical University School of Medicine, Yamanashi 409-3898, Japan.
Gut. 2002 Jun;50(6):790-6. doi: 10.1136/gut.50.6.790.
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.
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.
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.
Cajal间质细胞（ICC）是胃肠平滑肌运动神经传递的起搏细胞和介质。ICC需要通过原癌基因c-Kit（一种受体酪氨酸激酶）进行细胞信号传导，以实现表型的发育和维持。许多证明ICC功能的证据来自对W/W（V）小鼠的研究，这些小鼠的Kit功能降低，特定ICC群体数量减少。本研究的目的是差异检测野生型和W/W（V）突变小鼠小肠中的基因表达。
使用差异基因显示方法分析野生型和W/W（V）突变体空肠的RNA。18个查询被鉴定为在野生型和W/W（V）小鼠中差异显示的新基因。一个候选基因，编码一种新型酸性磷酸酶样蛋白，在喂食和饥饿的W/W（V）小鼠中显著受抑制。小鼠基因及其人类对应物的全长克隆被命名为酸性磷酸酶样蛋白1（ACPL1）。人类ACPL1 cDNA编码一个428个氨基酸的蛋白质，与人类前列腺酸性磷酸酶蛋白具有同源性。该基因位于1q21。ACPL1在人类小肠和结肠中大量表达。在转染的COS-7细胞中发现基因产物位于细胞质中。逆转录-聚合酶链反应分析显示单个分离的ICC中存在ACPL1 mRNA表达。
基因分析表明，ACPL1在正常和W/W（V）小鼠的小肠中差异表达。小肠中的ICC表达ACPL1的mRNA。W/W（V）小鼠空肠中ACPL1的特异性下调以及在人类肠道组织中的高表达表明，ACPL1基因可能与小鼠和人类的ICC功能相关。
