Harding C O, Williams P, Pflanzer D M, Colwell R E, Lyne P W, Wolff J A
Department of Pediatrics, Waisman Center, University of Wisconsin-Madison 53705.
Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2644-8. doi: 10.1073/pnas.89.7.2644.
A mouse mutant with sarcosinemia was found by screening the progeny of ethylnitrosourea-mutagenized mice for aminoacidurias. Paper chromatography, column chromatography, and gas chromatography-mass spectrometry identified high levels of sarcosine in the urine of the mutant mice. While sarcosine cannot be detected in the urine of plasma of normal mice, the urinary sarcosine level of 102 +/- 58 mmol per g of creatinine in the mutant mice was at the upper range of the urinary levels (1.5-4.5 mmol of sarcosine per g of creatinine) observed in humans with sarcosinemia. Similarly, the plasma sarcosine level of 785 +/- 153 mumol/liter in the sarcosinemic mice was at the upper range of the plasma sarcosine levels (53-760 mumol/liter) observed in affected humans. Sarcosine dehydrogenase [sarcosine:(acceptor) oxidoreductase (demethylating), EC 1.5.99.1] activity was deficient in sarcosinemic mice. The sarcosinuria phenotype in these mice was inherited as an autosomal recessive trait. This mouse mutant provides a useful genetic model for human sarcosinemia and for development of therapeutic approaches for genetic disease.
通过对用乙基亚硝基脲诱变的小鼠后代进行氨基酸尿症筛查，发现了一种患有肌氨酸血症的小鼠突变体。纸色谱法、柱色谱法和气相色谱 - 质谱法鉴定出突变小鼠尿液中肌氨酸水平很高。正常小鼠的尿液和血浆中检测不到肌氨酸，但突变小鼠每克肌酐中尿肌氨酸水平为102±58 mmol，处于患有肌氨酸血症的人类所观察到的尿液水平范围（每克肌酐含1.5 - 4.5 mmol肌氨酸）的上限。同样，患肌氨酸血症小鼠的血浆肌氨酸水平为785±153 μmol/升，处于受影响人类所观察到的血浆肌氨酸水平范围（53 - 760 μmol/升）的上限。肌氨酸脱氢酶[sarcosine:(acceptor) oxidoreductase (demethylating), EC 1.5.99.1]活性在患肌氨酸血症的小鼠中缺乏。这些小鼠的肌氨酸尿表型作为常染色体隐性性状遗传。这种小鼠突变体为人类肌氨酸血症以及遗传疾病治疗方法的开发提供了一个有用的遗传模型。
