Nprl3 is required for normal development of the cardiovascular system

作者：Kowalczyk Monika S; Hughes Jim R; Babbs Christian; Sanchez Pulido Luis; Szumska Dorota; Sharpe Jacqueline A; Sloane Stanley Jacqueline A; Morriss Kay Gillian M; Smoot Leslie B; Roberts Amy E; Watkins Hugh; Bhattacharya Shoumo; Gibbons Richard J; Ponting Chris P; Wood William G; Higgs Douglas R^*

来源：Mammalian Genome, 2012, 23(7-8): 404-415.

DOI：10.1007/s00335-012-9398-y

C16orf35 is a conserved and widely expressed gene lying adjacent to the human alpha-globin cluster in all vertebrate species. In-depth sequence analysis shows that C16orf35 (now called NPRL3) is an orthologue of the yeast gene Npr3 (nitrogen permease regulator 3) and, furthermore, is a paralogue of its protein partner Npr2. The yeast Npr2/3 dimeric protein complex senses amino acid starvation and appropriately adjusts cell metabolism via the TOR pathway. Here we have analysed a mouse model in which expression of Nprl3 has been abolished using homologous recombination. The predominant effect on RNA expression appears to involve genes that regulate protein synthesis and cell cycle, consistent with perturbation of the mTOR pathway. Embryos homozygous for this mutation die towards the end of gestation with a range of cardiovascular defects, including outflow tract abnormalities and ventriculoseptal defects consistent with previous observations, showing that perturbation of the mTOR pathway may affect development of the myocardium. NPRL3 is a candidate gene for harbouring mutations in individuals with developmental abnormalities of the cardiovascular system.

• 出版日期2012-8