Generation of Calhm1 knockout mouse and characterization of calhm1 gene expression.
Alzheimer's disease (AD) is the most common neurodegenerative 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 promoter 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.
State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Junbing
J
Wu
Shengyi
S
Peng
Rong
R
Wu
Yumin
Y
Hao
Guangju
G
Ji
Zengqiang
Z
Yuan
D000818:Animals; D015220:Calcium Channels / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics
C575356:CALHM1 protein, mouse; D015220:Calcium Channels; D012333:RNA, Messenger