Cystathionine β-synthase-deficient mice thrive on a low-methionine diet
Cystathionine β-synthase-deficient mice thrive on a low-methionine diet
复制标题
DOI：
10.1096/fj.13-240770
复制
发表时间：
2014-02-01
期刊：
影响因子：
4.8
通讯作者：
Kruger, Warren D.
中科院分区：
文献类型：
--
作者：
Gupta, Sapna;Melnyk, Stepan B.;Kruger, Warren D.
半胱硫氨酸合成酶（CBS）缺乏症是一种以血清总同型半胱氨酸（tHcy）升高为特征的隐性先天性代谢错误。此前，我们的实验室开发了一种CBS缺乏症小鼠模型，TgI278T CBS(-)/(-)（缩写为CBS(-/-)），其特征是体重低、低脂肪、sd -1表达降低、面部脱发和骨质疏松。为了确定蛋氨酸限制饮食（MRD）的潜在益处，我们从断奶至240日龄给Cbs（-/-）和Cbs（+/-）对照小鼠喂食MRD或常规饮食（RD）。喂食MRD的Cbs（-/-）小鼠tHcy下降77%，体重增加28%，脂肪量增加130%，Scd-1表达增加82%，骨密度增加10.6%，并且完全没有喂食RD的年龄匹配Cbs（-/-）小鼠所观察到的脱发表型。在研究结束时，喂食MRD的Cbs（-/-）小鼠在表型上与喂食RD的Cbs（+/-）小鼠没有区别。值得注意的是，MRD饮食对Cbs（-/-）小鼠非常有益。对Cbs（+/-）小鼠则几乎相反。这些研究表明，低蛋氨酸饮食可以纠正CBS缺失的表型后果，并提供了基因型和饮食如何相互作用影响哺乳动物表型的显著例子。Gupta， S., Melnyk, s.b., Kruger， W.D.半胱硫氨酸合酶缺陷小鼠在低蛋氨酸饮食中茁壮成长。
Cystathionine -synthase (CBS) deficiency is a recessive inborn error of metabolism characterized by elevated serum total homocysteine (tHcy). Previously, our laboratory developed a mouse model of CBS deficiency, TgI278T Cbs(-)/(-) (abbreviated as Cbs(-/-)), characterized by low weight, low adiposity, decreased Scd-1 expression, facial alopecia, and osteoporosis. To determine the potential benefit of a methionine-restricted diet (MRD), we fed Cbs(-/-) and Cbs(+/-) control mice either an MRD or a regular diet (RD) from weaning till 240 d of age. Cbs(-/-) mice fed the MRD had a 77% decrease in tHcy, 28% increase in weight, 130% increase in fat mass, 82% increase in Scd-1 expression, and 10.6% increase in bone density and entirely lacked the alopecia phenotype observed in age-matched Cbs(-/-) mice fed the RD. At the end of the study, Cbs(-/-) mice fed the MRD were phenotypically indistinguishable from Cbs(+/-) mice fed the RD. Notably, whereas the MRD diet was highly beneficial to Cbs(-/-) mice, it had nearly opposite effect on Cbs(+/-) mice. These studies show that a low-methionine diet can correct the phenotypic consequences of loss of CBS and provide a striking example of how genotype and diet can interact to influence phenotype in mammals.Gupta, S., Melnyk, S.B., Kruger, W.D. Cystathionine -synthase-deficient mice thrive on a low-methionine diet.