Polycystic kidneys and chronic inflammatory lesions are the delayed consequences of loss of the suppressor of cytokine signaling-1 (SOCS-1)
Details
Publication Year 2002-01-22, Volume 99, Issue #2, Page 943-948
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type
Journal Article
Abstract
Mice with inactivation of the gene encoding the suppressor of cytokine signaling-1 (SOCS-1) die in neonatal life with an IFN-gamma-dependent inflammatory disease dominated by fatty degeneration and necrosis of the liver. To establish the long-term pathological consequences of loss of SOCS-1 in mice, where initial survival was made possible by also deleting the IFN-gamma gene, a comparison was made of the lifespan of groups of SOCS-1(-/-) IFN-gamma(-/-), SOCS-1(+/+) IFN-gamma(-/-) and SOCS-1(+/+) IFN-gamma(+/+) mice. Mice lacking the genes for both SOCS-1 and IFN-gamma exhibited an accelerated death rate compared with control groups. Disease states developing selectively in SOCS-1(-/-) IFN-gamma(-/-) mice were polycystic kidneys, pneumonia, chronic skin ulcers, and chronic granulomas in the gut and various other organs. Mice of all three groups developed cataracts, but disease development was accelerated in the groups lacking IFN-gamma. SOCS-1(-/-) IFN-gamma(-/-) mice exhibited a slightly increased predisposition to the development of T lymphoid leukemia, either spontaneous or radiation-induced. The development of polycystic kidneys may be caused by a developmental defect in renal-tubule organization noted in neonatal SOCS-1(-/-) mice. The chronic infections and granulomas of SOCS-1(-/-) IFN-y(-/-) mice may be based on autoaggression of SOCS-1(-/-) T lymphoid and related cells or a functional deficiency of these cells when lacking SOCS-1.
Publisher
NATL ACAD SCIENCES
Keywords
TRANSGENIC MICE; BOX MOTIF; PROTEINS; GAMMA; TRANSDUCTION; INHIBITION; RECEPTOR; MECHANISM; LACKING; DOMAIN
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2002-01-22 12:00:00
Last Modified: 0001-01-01 12:00:00
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