Matera I, De Miguel-Rodríguez M, Fernández-Santos J M, Santamaria G, Puliti A, Ravazzolo R, Romeo G, Galera-Davidson H, Ceccherini I
Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, 16148 Genova, Italy.
DNA Seq. 2000;11(5):405-17. doi: 10.3109/10425170009033991.
The RET proto-oncogene, a member of the Receptor Tyrosine Kinase family, plays a crucial role during the development of the excretory system and the enteric nervous system, as demonstrated by in vivo animal studies and by its involvement in the pathogenesis of several human neurocristopathies like Hirschsprung disease and Multiple Endocrine Neoplasia type 2. Using a multistep RT-PCR approach we have isolated and sequenced the cDNA of the whole rat RET proto-oncogene, reporting the deduced amino acid sequence in comparison with the human and mouse counterparts. Moreover, two different isoforms (RET9 and RET51) have been confirmed in the rat, while a third RET isoform demonstrated in human (RET43) has not resulted to be conserved in this species. Finally, we have determined the genomic structure of the rat RET proto-oncogene comparing the exon-intron boundaries and intron sizes with the known structure of the human homologous gene. Our findings will facilitate the molecular study of appropriate rat models of RET related human diseases.
RET原癌基因是受体酪氨酸激酶家族的成员之一，体内动物研究以及其在诸如先天性巨结肠和2型多发性内分泌肿瘤等几种人类神经嵴病发病机制中的作用表明，它在排泄系统和肠神经系统的发育过程中起着至关重要的作用。我们采用多步RT-PCR方法分离并测序了大鼠整个RET原癌基因的cDNA，并报告了推导的氨基酸序列，同时与人类和小鼠的对应序列进行了比较。此外，在大鼠中已证实存在两种不同的异构体（RET9和RET51），而在人类中发现的第三种RET异构体（RET43）在该物种中未得到保守。最后，我们确定了大鼠RET原癌基因的基因组结构，将外显子-内含子边界和内含子大小与人类同源基因的已知结构进行了比较。我们的研究结果将有助于对RET相关人类疾病的合适大鼠模型进行分子研究。
