Differentially expressed genes in transgenic mice carrying human mutant presenilin-2 (N141I): correlation of selenoprotein M with Alzheimer's disease.
Mutations in genes for Alzheimer's disease (AD) result in a modulating of gene expressions in the brains of patients with AD. The aim of this study was to identify genes whose expression is modulated due to the over-expression of human mutant presenilin-2 (N141I) (hPS2m) in transgenic mice, which has previously been produced by us. To test this, GeneFishing DEG101 technique was performed on large-scale screen of mRNA from transgenic and non-transgenic brains. A total of 40 transcriptional products corresponding to cDNA were compared between two brains, and 17 showed a differential expression between the samples in all sets of experiments. However, all showed significant homology to known genes. Initially, a cloning corresponding to human selenoprotein M (hSelM) was chosen for investigation further because SelM induced by sodium selenite, a pro-oxidant, may have a functional role in catalyze the free radicals. We found that mouse SelM had significantly suppressed on its transcriptional products in transgenic brains. In parallel, suppression of endogenous was not observed in transgenic brains. Moreover, the levels of green fluorescence on hSelM fusion protein with EGFP were suppressed in the cells transfected with hPS2m, and its levels had actually increased by treatments of sodium selenite. Thus, the results indicate that SelM might play a suppressive or protective role in the pathology of patients with AD and it will be necessary to investigate further on functional roles of other up- and down-regulated gene in future.
Hwang
Dae Y
DY
Division of Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA, 5 Nokbun-dong Eunpyng-ku, 122-704, Seoul, Korea.
Cho
Jung S
JS
Oh
Jae H
JH
Shim
Sun B
SB
Jee
Seung W
SW
Lee
Su H
SH
Seo
Su J
SJ
Lee
Sang-Koo
SK
Lee
Seok H
SH
Kim
Yong K
YK
D000544:Alzheimer Disease / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053766:Presenilin-2; D012333:RNA, Messenger / Q000235:genetics; D051140:Selenoproteins / Q000235:genetics*; D018038:Sodium Selenite / Q000494:pharmacology
D017931:DNA Primers; D008565:Membrane Proteins; C508861:PSEN2 protein, human; D053766:Presenilin-2; D012333:RNA, Messenger; C448999:SELM protein, human; D051140:Selenoproteins; D018038:Sodium Selenite