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Adenosine-deaminase-deficient mice die perinatally and exhibit liver-cell degeneration, atelectasis and small intestinal cell death.

Publication ,  Journal Article
Migchielsen, AA; Breuer, ML; van Roon, MA; te Riele, H; Zurcher, C; Ossendorp, F; Toutain, S; Hershfield, MS; Berns, A; Valerio, D
Published in: Nat Genet
July 1995

We report the generation and characterization of mice lacking adenosine deaminase (ADA). In humans, absence of ADA causes severe combined immunodeficiency. In contrast, ADA-deficient mice die perinatally with marked liver-cell degeneration, but lack abnormalities in the thymus. The ADA substrates, adenosine and deoxyadenosine, are increased in ADA-deficient mice. Adenine deoxyribonucleotides are only modestly elevated, whereas S-adenosylhomocysteine hydrolase activity is reduced more than 85%. Consequently, the ratio of S-adenosylhomocysteine (AdoMet) to S-adenosyl homocysteine (AdoHcy) is reduced threefold in liver. We conclude that ADA plays a more critical role in murine than human fetal development. The murine liver pathology may be due to AdoHcy-mediated inhibition of AdoMet-dependent transmethylation reactions.

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Published In

Nat Genet

DOI

ISSN

1061-4036

Publication Date

July 1995

Volume

10

Issue

3

Start / End Page

279 / 287

Location

United States

Related Subject Headings

  • T-Lymphocyte Subsets
  • Severe Combined Immunodeficiency
  • Purines
  • Pulmonary Atelectasis
  • Pregnancy
  • Mutation
  • Molecular Sequence Data
  • Mice
  • Methylation
  • Male
 

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Migchielsen, A. A., Breuer, M. L., van Roon, M. A., te Riele, H., Zurcher, C., Ossendorp, F., … Valerio, D. (1995). Adenosine-deaminase-deficient mice die perinatally and exhibit liver-cell degeneration, atelectasis and small intestinal cell death. Nat Genet, 10(3), 279–287. https://doi.org/10.1038/ng0795-279
Migchielsen, A. A., M. L. Breuer, M. A. van Roon, H. te Riele, C. Zurcher, F. Ossendorp, S. Toutain, M. S. Hershfield, A. Berns, and D. Valerio. “Adenosine-deaminase-deficient mice die perinatally and exhibit liver-cell degeneration, atelectasis and small intestinal cell death.Nat Genet 10, no. 3 (July 1995): 279–87. https://doi.org/10.1038/ng0795-279.
Migchielsen AA, Breuer ML, van Roon MA, te Riele H, Zurcher C, Ossendorp F, et al. Adenosine-deaminase-deficient mice die perinatally and exhibit liver-cell degeneration, atelectasis and small intestinal cell death. Nat Genet. 1995 Jul;10(3):279–87.
Migchielsen, A. A., et al. “Adenosine-deaminase-deficient mice die perinatally and exhibit liver-cell degeneration, atelectasis and small intestinal cell death.Nat Genet, vol. 10, no. 3, July 1995, pp. 279–87. Pubmed, doi:10.1038/ng0795-279.
Migchielsen AA, Breuer ML, van Roon MA, te Riele H, Zurcher C, Ossendorp F, Toutain S, Hershfield MS, Berns A, Valerio D. Adenosine-deaminase-deficient mice die perinatally and exhibit liver-cell degeneration, atelectasis and small intestinal cell death. Nat Genet. 1995 Jul;10(3):279–287.

Published In

Nat Genet

DOI

ISSN

1061-4036

Publication Date

July 1995

Volume

10

Issue

3

Start / End Page

279 / 287

Location

United States

Related Subject Headings

  • T-Lymphocyte Subsets
  • Severe Combined Immunodeficiency
  • Purines
  • Pulmonary Atelectasis
  • Pregnancy
  • Mutation
  • Molecular Sequence Data
  • Mice
  • Methylation
  • Male