{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:59:31Z","timestamp":1793393971659,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,6,8]],"date-time":"2010-06-08T00:00:00Z","timestamp":1275955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Severe deficiency of methylenetetrahydrofolate reductase (MTHFR) with homocystinuria can result in early demise or later\u2010onset neurological impairment, including developmental delay, motor dysfunction, and seizures. We previously characterized BALB\/c <jats:italic>Mthfr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice as a model for this disorder and have recently backcrossed the disrupted allele onto the C57Bl\/6 background to examine the variable phenotypes in MTHFR deficiency. Compared with BALB\/c <jats:italic>Mthfr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice, C57Bl\/6 <jats:italic>Mthfr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice have enhanced survival rates (81% vs 26.5%). Four\u2010day\u2010old BALB\/c mutant pups had lower body, brain, and spleen weights relative to their wild\u2010type counterparts compared with C57Bl\/6 mutants. Pregnant BALB\/c <jats:italic>Mthfr<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>mice had increased resorptions and embryonic delays compared with wild\u2010type littermates, whereas these outcomes in C57Bl\/6 c <jats:italic>Mthfr<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>mice were similar to those of wild\u2010type C57Bl\/6 mice. BALB\/c\u2010mutant pups had altered hematological profiles (higher hematocrit, hemoglobin, and white blood cell counts, with lower platelet counts) compared with C57Bl\/6 mutants. Mutants of both strains had similar degrees of hepatic steatosis, hepatic activity of betaine:homocysteine methyltransferase, and altered cerebellar histology. Electroretinograms (ERG) in C57Bl\/6 <jats:italic>Mthfr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice revealed decreased amplitude of scotopic and photopic waves in 6\u2010week\u2010old mice, with normalized ERGs at 13 weeks. Plasma homocysteine was modestly higher in C57Bl\/6 compared with BALB\/c mice. Our results emphasize the variable presentation of MTHFR deficiency in different genetic backgrounds and suggest that plasma homocysteine is not a predictor of severity. In addition, our novel findings of decreased spleen weights, thrombocytopenia, and impaired retinal function warrant investigation in patients with severe MTHFR deficiency or other forms of homocystinuria.<\/jats:p>","DOI":"10.1007\/s10545-010-9127-1","type":"journal-article","created":{"date-parts":[[2010,6,7]],"date-time":"2010-06-07T11:31:34Z","timestamp":1275910294000},"page":"147-157","source":"Crossref","is-referenced-by-count":28,"title":["Complete deficiency of methylenetetrahydrofolate reductase in mice is associated with impaired retinal function and variable mortality, hematological profiles, and reproductive outcomes"],"prefix":"10.1002","volume":"34","author":[{"given":"Andrea K.","family":"Lawrance","sequence":"first","affiliation":[{"name":"Departments of Human Genetics, Pediatrics, and Biology McGill University\u2013Montreal Children's Hospital Research Institute 4060 Ste. 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