Indo Y, Mardy S, Tsuruta M, Karim M A, Matsuda I
Department of Pediatrics, Kumamoto University School of Medicine, Japan.
Jpn J Hum Genet. 1997 Jun;42(2):343-51. doi: 10.1007/BF02766957.
Nerve growth factor (NGF) induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons. TRKA, a receptor tyrosine kinase cloned from a human colon cancer was later found to be expressed in the nervous system and phosphorylated in response to NGF. Somatic rearrangement(s) of the TRKA gene (also designated NTRK1) are responsible for formation of some oncogenes. Genetic defects in TRKA are responsible for a human disorder, congenital insensitivity to pain with anhidrosis (CIPA). We report here isolation and characterization of the TRKA gene which spans at least 23 kb and is split into 17 exons. Exon sizes range from 18 to 394 bp and intron sizes range from 170 bp to at least 3.3 kb. Sizes and boundaries of the exons were determined, and all the splice donor and acceptor sites conformed to the GT/AG rule. Approximately 1.2 kb of the 5'-flanking regions was sequenced, and putative regulatory elements were identified. These results will be useful for studies on the developmental and biological regulation of the TRKA gene and for further characterization of mutations in CIPA patients as well as elucidation of mechanisms responsible for rearrangement(s) observed in human tumors.
神经生长因子（NGF）可诱导神经突生长，并促进胚胎感觉神经元和交感神经元的存活。TRKA是一种从人类结肠癌中克隆出的受体酪氨酸激酶，后来发现它在神经系统中表达，并在NGF作用下发生磷酸化。TRKA基因（也称为NTRK1）的体细胞重排是某些癌基因形成的原因。TRKA基因的遗传缺陷导致一种人类疾病，即先天性无痛无汗症（CIPA）。我们在此报告TRKA基因的分离和特征，该基因跨度至少23 kb，分为17个外显子。外显子大小从18到394 bp不等，内含子大小从170 bp到至少3.3 kb不等。确定了外显子的大小和边界，所有剪接供体和受体位点均符合GT/AG规则。对约1.2 kb的5'侧翼区域进行了测序，并鉴定了推定的调控元件。这些结果将有助于研究TRKA基因的发育和生物学调控，进一步鉴定CIPA患者的突变特征，以及阐明在人类肿瘤中观察到的重排机制。
