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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Migchielsen, AA; Breuer, ML; van Roon, MA; te Riele, H; Zurcher, C; Ossendorp, F; Toutain, S; Hershfield, MS; Berns, A; Valerio, D

Published Date

  • July 1995

Published In

Volume / Issue

  • 10 / 3

Start / End Page

  • 279 - 287

PubMed ID

  • 7670465

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng0795-279

Language

  • eng

Conference Location

  • United States