The methylenetetrahydrofolate reductase (Mthfr) gene maps to distal mouse chromosome 4.

Abstract

Species: Mouse Locus name: 5,10-Methylenetetrahydrofolate reductase Locus symbol: Mthfr Map position: Distal Chromosome (Chr) 4, Cen t romere D4Mit13-1.06 cM _+ 0.75-Mthfr-l.06 +_ 1.06-D4Mit42 Method of mapping: Mthfr was localized by RFLP analysis of 94 animals from an interspecific backcross panel ((C57BL/6JEi x SPRET/Ei)F 1 x SPRET/Ei) provided by The Jackson Laboratory, Bar Harbor, Me. (BSS panel) [1]. To verify the localization, RFLP analysis was performed on 94 animals from the reciprocal cross ((C57BL/6J x Mus spretus)F 1 x C57BL/6J) (BSB panel) (Fig. 1) [1]. Database deposit information: The data are available from the Mouse Genome Database, accession number MGD-CREX-672. Molecular reagents: A 727-bp mouse cDNA was obtained by reverse transcription/PCR of mouse brain RNA, with primer sequences based on sequence data of a mouse genomic clone (Pai et al. unpublished). The 5' primer (5 ' -ATGGTGAACGAGGCCAGAGGAA-3' ) began at the ATG translation initiation start site, and the 3' primer (5 ' -GCAGGCCTTCACAAAGCTGAAGA-3' ) ended at bp 727 of the mouse cDNA. Sequence analysis verified the identity of the PCR product (Frosst, results not shown). The mouse cDNA was labeled by random priming and hybridized to Southern blots of TaqI-digested mouse genomic DNA. Allele detection: Allele detection was performed by RFLP analysis of a TaqI polymorphism. The C57BL/6J strain has an allele of approximately 6.5 kb, while the Mus spretus strain has an allele of approximately 4.2 kb. A constant band of approximately 3.3 kb was seen in both strains. Previously identified homologs: Human MTHFR has been mapped to the p36.3-p36.2 region of Chr 1 by in situ hybridization [2]. Discussion: M T H F R cata lyzes the conve r s ion of 5,10methylenetetrahydrofolate to 5-methyltetrahydrofolate, the primary circulatory form of folate. 5-Methyltetrahydrofolate serves as the carbon donor for homocysteine remethylation to methionine. Recently, a common mutation in MTHFR (a C ~ T substitution at bp 677 resulting in an alanine to valine missense mutation) was proposed as a genetic risk factor for neural tube defects in man [3,4,5]. This mutation requires low folate status in plasma for the development of mild hyperhomocysteinemia [6]. This genetic-nutrient interactive effect is consistent with the multifactorial model for neural tube defects and with the established role of folic acid in reducing the recurrence and occurrence of this developmental anomaly. The curly-tail (cO mouse is a mouse model for neural tube defects; it is thought to closely mimic the human disorder with