Alzheimer’s disease(AD)is the most common neurode-generative disease among elderly people worldwide.Several genes have been validated to be associated with AD,and calcium homeostasis modulator 1(Calhm1)is the latest ...Alzheimer’s disease(AD)is the most common neurode-generative disease among elderly people worldwide.Several genes have been validated to be associated with AD,and calcium homeostasis modulator 1(Calhm1)is the latest suspected one.To investigate the biological and pathological function of Calhm1 systematically,we generated a Calhm1 conventional knockout mouse.However,both the male and female of elderly Calhm1 knockout(KO)mice showed similar ability to their wild type littermates in spatial learning and memory retrieving.Surprisingly,we found that Calhm1 mRNA could not be detected in mouse brains at different ages,although it is expressed in the human brain tissues.We further found that CpG islands(CGIs)of both mouse and human Calhm1 were hypermethylated,whereas CGI of mouse Calhm2 was hypomethylated.In addition,transcriptional active marker H3K4Di occupied on promoters of human Calhm1 and mouse Calhm2 at a considerable level in brain tissues,while the occupancy of H3K4Di on pro-moter of mouse Calhm1 was rare.In sum,we found that mouse Calhm1 was of rare abundance in brain tissues.So it might not be suitable to utilize the knockout murine model to explore biological function of Calhm1 in the pathogenesis of AD.展开更多
基金supported by the National Basic Research Program(973 Program)(Grant No.2009CB918704)the National Natural Science Foundation of China(Grant Nos.81125010 and 81030025).
文摘Alzheimer’s disease(AD)is the most common neurode-generative disease among elderly people worldwide.Several genes have been validated to be associated with AD,and calcium homeostasis modulator 1(Calhm1)is the latest suspected one.To investigate the biological and pathological function of Calhm1 systematically,we generated a Calhm1 conventional knockout mouse.However,both the male and female of elderly Calhm1 knockout(KO)mice showed similar ability to their wild type littermates in spatial learning and memory retrieving.Surprisingly,we found that Calhm1 mRNA could not be detected in mouse brains at different ages,although it is expressed in the human brain tissues.We further found that CpG islands(CGIs)of both mouse and human Calhm1 were hypermethylated,whereas CGI of mouse Calhm2 was hypomethylated.In addition,transcriptional active marker H3K4Di occupied on promoters of human Calhm1 and mouse Calhm2 at a considerable level in brain tissues,while the occupancy of H3K4Di on pro-moter of mouse Calhm1 was rare.In sum,we found that mouse Calhm1 was of rare abundance in brain tissues.So it might not be suitable to utilize the knockout murine model to explore biological function of Calhm1 in the pathogenesis of AD.
