Cystathionine beta-synthase null homocystinuric mice fail to exhibit altered hemostasis or lowering of plasma homocysteine in response to betaine treatment.

Molecular Genetics and Metabolism
Kenneth N MacleanJan P Kraus

Abstract

Cystathionine beta-synthase (CBS) deficient homocystinuria is an inherited metabolic defect that if untreated typically results in mental retardation, thromboembolism and a range of connective tissue disturbances. A knockout mouse model has previously been used to investigate pathogenic mechanisms in classical homocystinuria (Watanabe et al., PNAS 92 (1995) 1585-1589). This mouse model exhibits a semi-lethal phenotype and the majority of mice do not survive the early neonatal period. We report here that the birth incidence of cbs (-/-) mice produced from heterozygous crosses is non-Mendelian and not significantly improved by treatment with either the Hcy lowering compound betaine or the cysteine donor N-acetylcysteine. Betaine treatment did improve survival of cbs (-/-) mice and restored fertility to female cbs (-/-) mice but did so without significantly lowering Hcy levels. Surviving cbs (-/-) mice failed to show any alteration in coagulation parameters compared to wild-type controls. Moribund cbs (-/-) mice exhibited severe liver injury and hepatic fibrosis while surviving cbs (-/-) mice although less severely affected, still exhibited a level of severe liver injury that is not found in the human disease. The hepatopathy obse...Continue Reading

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Citations

Apr 16, 2014·Antioxidants & Redox Signaling·Mark R HellmichCsaba Szabo
Sep 7, 2017·Antioxidants & Redox Signaling·Tomas MajtanJan P Kraus
Oct 21, 2018·British Journal of Pharmacology·Viktor KožichPeter Nagy
Jul 24, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Renfei LuoChunling Li
Jun 4, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hua JiangKenneth N Maclean
Aug 20, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tomas MajtanJan P Kraus
Nov 5, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kenneth N MacleanJames R Roede
Aug 28, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tomas MajtanJan P Kraus
Feb 16, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kenneth N MacleanSally P Stabler
May 10, 2020·The FEBS Journal·Sibel Cal-KayitmazbatirIbrahim Halil Kavakli
Feb 11, 2011·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·S Harvey Mudd
May 18, 2016·The Journal of Clinical Investigation·Erez M BublilJan P Kraus
Aug 21, 2020·Reproductive Sciences·Damian D GuerraK Joseph Hurt
May 6, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sapna GuptaWarren D Kruger

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Methods Mentioned

BETA
genotyping
biopsies
PCR
dissection
electron microscopy

Software Mentioned

Prophet

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