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. 1992 Apr 1;89(7):2644–2648. doi: 10.1073/pnas.89.7.2644

sar: a genetic mouse model for human sarcosinemia generated by ethylnitrosourea mutagenesis.

C O Harding 1, P Williams 1, D M Pflanzer 1, R E Colwell 1, P W Lyne 1, J A Wolff 1
PMCID: PMC48718  PMID: 1372986

Abstract

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.

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Selected References

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  1. Bennett M. J., Curnock D. A., Engel P. C., Shaw L., Gray R. G., Hull D., Patrick A. D., Pollitt R. J. Glutaric aciduria type II: biochemical investigation and treatment of a child diagnosed prenatally. J Inherit Metab Dis. 1984;7(2):57–61. doi: 10.1007/BF01805802. [DOI] [PubMed] [Google Scholar]
  2. Blom W., Fernandes J. Folic acid dependent hypersarcosinaemia. Clin Chim Acta. 1979 Jan 15;91(2):117–125. doi: 10.1016/0009-8981(79)90445-5. [DOI] [PubMed] [Google Scholar]
  3. COLEMAN D. L. Phenylalanine hydroxylase activity in dilute and nondilute strains of mice. Arch Biochem Biophys. 1960 Dec;91:300–306. doi: 10.1016/0003-9861(60)90504-x. [DOI] [PubMed] [Google Scholar]
  4. Capecchi M. R. The new mouse genetics: altering the genome by gene targeting. Trends Genet. 1989 Mar;5(3):70–76. doi: 10.1016/0168-9525(89)90029-2. [DOI] [PubMed] [Google Scholar]
  5. Chapman V. M., Miller D. R., Armstrong D., Caskey C. T. Recovery of induced mutations for X chromosome-linked muscular dystrophy in mice. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1292–1296. doi: 10.1073/pnas.86.4.1292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Copeland N. G., Jenkins N. A. Development and applications of a molecular genetic linkage map of the mouse genome. Trends Genet. 1991 Apr;7(4):113–118. doi: 10.1016/0168-9525(91)90455-y. [DOI] [PubMed] [Google Scholar]
  7. Gerritsen T., Waisman H. A. Hypersarcosinemia: an inborn error of metabolism. N Engl J Med. 1966 Jul 14;275(2):66–69. doi: 10.1056/NEJM196607142750202. [DOI] [PubMed] [Google Scholar]
  8. Glorieux F. H., Scriver C. R., Delvin E., Mohyuddin F. Transport and metabolism of sarcosine in hypersarcosinemic and normal phenotypes. J Clin Invest. 1971 Nov;50(11):2313–2322. doi: 10.1172/JCI106729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goodman S. I., McCabe E. R., Fennessey P. V., Mace J. W. Multiple acyl-CoA dehydrogenase deficiency (glutaric aciduria type II) with transient hypersarcosinemia and sarcosinuria; possible inherited deficiency of an electron transfer flavoprotein. Pediatr Res. 1980 Jan;14(1):12–17. doi: 10.1203/00006450-198001000-00004. [DOI] [PubMed] [Google Scholar]
  10. HOSKINS D. D., BJUR R. A. THE OXIDATION OF N-METHYLGLYCINES BY PRIMATE LIVER MITOCHONDRIA. ASSAY, PURIFICATION, AND CHARACTERIZATION OF SARCOSINE DEHYDROGENASE. J Biol Chem. 1964 Jun;239:1856–1863. [PubMed] [Google Scholar]
  11. Hoffmann G., Aramaki S., Blum-Hoffmann E., Nyhan W. L., Sweetman L. Quantitative analysis for organic acids in biological samples: batch isolation followed by gas chromatographic-mass spectrometric analysis. Clin Chem. 1989 Apr;35(4):587–595. [PubMed] [Google Scholar]
  12. King T. R., Dove W. F., Herrmann B., Moser A. R., Shedlovsky A. Mapping to molecular resolution in the T to H-2 region of the mouse genome with a nested set of meiotic recombinants. Proc Natl Acad Sci U S A. 1989 Jan;86(1):222–226. doi: 10.1073/pnas.86.1.222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kuehn M. R., Bradley A., Robertson E. J., Evans M. J. A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice. Nature. 1987 Mar 19;326(6110):295–298. doi: 10.1038/326295a0. [DOI] [PubMed] [Google Scholar]
  14. Lemieux B., Auray-Blais C., Giguère R., Shapcott D., Scriver C. R. Newborn urine screening experience with over one million infants in the Quebec Network of Genetic Medicine. J Inherit Metab Dis. 1988;11(1):45–55. doi: 10.1007/BF01800056. [DOI] [PubMed] [Google Scholar]
  15. Levy H. L., Coulombe J. T., Benjamin R. Massachusetts Metabolic Disorders Screening Program: III. Sarcosinemia. Pediatrics. 1984 Oct;74(4):509–513. [PubMed] [Google Scholar]
  16. McDonald J. D., Bode V. C., Dove W. F., Shedlovsky A. Pahhph-5: a mouse mutant deficient in phenylalanine hydroxylase. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1965–1967. doi: 10.1073/pnas.87.5.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McDonald J. D., Bode V. C. Hyperphenylalaninemia in the hph-1 mouse mutant. Pediatr Res. 1988 Jan;23(1):63–67. doi: 10.1203/00006450-198801000-00014. [DOI] [PubMed] [Google Scholar]
  18. Minami R., Olek K., Wardenbach P. Hypersarcosinemia with craniostenosis-syndactylism syndrome. Humangenetik. 1975 Jun 19;28(2):167–171. doi: 10.1007/BF00735751. [DOI] [PubMed] [Google Scholar]
  19. Mudd S. H., Ebert M. H., Scriver C. R. Labile methyl group balances in the human: the role of sarcosine. Metabolism. 1980 Aug;29(8):707–720. doi: 10.1016/0026-0495(80)90192-4. [DOI] [PubMed] [Google Scholar]
  20. Scott C. R., Clark S. H., Teng C. C., Swedberg K. R. Clinical and cellular studies of sarcosinemia. J Pediatr. 1970 Nov;77(5):805–811. doi: 10.1016/s0022-3476(70)80239-6. [DOI] [PubMed] [Google Scholar]
  21. Shedlovsky A., Guenet J. L., Johnson L. L., Dove W. F. Induction of recessive lethal mutations in the T/t-H-2 region of the mouse genome by a point mutagen. Genet Res. 1986 Apr;47(2):135–142. doi: 10.1017/s0016672300022977. [DOI] [PubMed] [Google Scholar]
  22. Smith P. K., Krohn R. I., Hermanson G. T., Mallia A. K., Gartner F. H., Provenzano M. D., Fujimoto E. K., Goeke N. M., Olson B. J., Klenk D. C. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985 Oct;150(1):76–85. doi: 10.1016/0003-2697(85)90442-7. [DOI] [PubMed] [Google Scholar]
  23. Sweetman L., Nyhan W. L., Tauner D. A., Merritt T. A., Singh M. Glutaric aciduria Type II. J Pediatr. 1980 Jun;96(6):1020–1026. doi: 10.1016/s0022-3476(80)80629-9. [DOI] [PubMed] [Google Scholar]
  24. Tippett P., Danks D. M. The clinical and biochemical findings in three cases of hypersarcosinemia and one case of transient hypersarcosinuria associated with folic acid deficiency. Helv Paediatr Acta. 1974 Aug;29(3):261–267. [PubMed] [Google Scholar]
  25. Willems C., Heusden A., Hainaut A., Chapelle P. Hypersarcosinémie avec sarcosinurie. Etude d'une nouvelle famille. J Genet Hum. 1971 Mar;19(1):101–118. [PubMed] [Google Scholar]

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