Adenosine-deaminase-deficient mice die perinatally and exhibit liver-cell degeneration, atelectasis and small intestinal cell death.
Nat Genet
; 10(3): 279-87, 1995 Jul.
Article
en En
| MEDLINE
| ID: mdl-7670465
ABSTRACT
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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Banco de datos:
MEDLINE
Asunto principal:
Atelectasia Pulmonar
/
Adenosina Desaminasa
/
Intestino Delgado
/
Hígado
Tipo de estudio:
Etiology_studies
Límite:
Animals
/
Female
/
Humans
/
Male
/
Pregnancy
Idioma:
En
Año:
1995
Tipo del documento:
Article