title: Multiple single-nucleotide polymorphisms in the methylenetetrahydrofolate reductase and its truncated pseudogene of 23 inbred strains of mice.
abstract: Reduced 5,10-methylenetetrahydrofolate reductase (MTHFR) results in a number of human diseases. To find a model mouse sensitive to these diseases, we analyzed single-nucleotide polymorphisms (SNPs) of the mouse Mthfr using 23 phylogenetically distant strains of mouse. We found five SNPs: two nonsynonymous and three synonymous. The CAST/Ei strain has the nonsynonymous SNP L350V and five strains (NMRI, KJR, SWN2, MSM, and JF1) have the nonsynonymous SNP S22G. The MTHFR activity of CAST/Ei and MSM showed no significant difference in activity or thermostability compared with that of C57BL/6J. We also found a pseudogene segment of the mouse Mthfr that was not present in human and was more frequently variable than the functional gene. These results suggest a possibility that the truncated pseudogene may buffer variations of the mouse Mthfr functional gene, and the mouse has evolved fewer variations of the gene than human.
authors.affiliation: Department of Pathology, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Takeya
authors.forename: Mariko
authors.initials: M
authors.lastname: Esumi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shiroishi
authors.forename: Ryohei
authors.initials: R
authors.lastname: Hishida
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004789:Enzyme Activation; D004795:Enzyme Stability; D019143:Evolution, Molecular; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D006801:Humans; D045102:Methylenetetrahydrofolate Dehydrogenase (NAD+) / Q000737:chemistry* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011544:Pseudogenes / Q000235:genetics*; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013696:Temperature
chemical_list: D045102:Methylenetetrahydrofolate Dehydrogenase (NAD+)