Differentially Expressed Genes in Transgenic Mice Carrying Human Mutant Presenilin-2 (N141I): Correlation of Selenoprotein M with Alzheimer’s Disease

Abstract

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.

Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat

“…M. Muller et al (9) showed that this protein plays a major role in spicule formation in the demosponge Suberites domuncula. In addition, Hwang et al (10) suggested that SelM might play a suppressive or protective role in the pathology of patients with Alzheimer's disease. However, no transgenic rat expressing human SelM under the control of the human cytomegalovirus (CMV) immediate early promoter has been available for use in the study of the function of SelM in vivo.…”

Deletion of Selenoprotein M Leads to Obesity without Cognitive Deficits

“…A prior study of transgenic mice overexpressing the human mutant gene presenilin-2 associated with familial Alzheimer disease found that SelM expression was significantly down-regulated, suggesting a potential neuroprotective function for SelM in the prevention of Alzheimer disease (24). Familial Alzheimer disease-linked presenilin-2 mutations have been observed to alter intracellular calcium homeostasis (25), and more recently presenilin-2 was shown to modulate calcium shuttling between the endoplasmic reticulum and mitochondria (26).…”

“…6D). No significant differences in average weekly food consumption were found for either genotype (F (1,24) ϭ 1.253, p Ͼ 0.05) or gender (F (1,24) ϭ 0.04904, p Ͼ 0.05). However, the two animals that consumed the most food during this 4-week period were female SelM KO mice.…”

“…6, E and F). The levels of gWAT (F (1,24) ϭ 50.31, p Ͻ 0.0001) and ingWAT (F (1,24) ϭ 32.28, p Ͻ 0.0001) were increased ϳ2-fold in both male and female SelM KO mice relative to wild-type controls.…”

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“…In mouse, SelM is moderately expressed in various tissues including the heart, lung, kidney, uterus, and placenta, and highly expressed in thyroid and brain (180). Interestingly, overexpression of the presenilin-2 (PS2) gene responsible for the early-onset Alzheimer's disease caused the suppression of SelM, but not SelP, in the brain of transgenic mice (152). Detailed studies of SelM in the brain are required to establish its function and potential involvement in disease.…”