Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death.
Journal:
Proc. Natl. Acad. Sci. U.S.A. 1993 JanAuthors:
Kulkarni AB, Huh CG, Becker D, Geiser A, Lyght M, Flanders KC, Roberts AB, Sporn MB, Ward JM, Karlsson S
Abstract
To delineate specific developmental roles of transforming growth factor beta 1 (TGF-beta 1) we have disrupted its cognate gene in mouse embryonic stem cells by homologous recombination to generate TGF-beta 1 null mice. These mice do not produce detectable amounts of either TGF-beta 1 RNA or protein. After normal growth for the first 2 weeks they develop a rapid wasting syndrome and die by 3-4 weeks of age. Pathological examination revealed an excessive inflammatory response with massive infiltra
...[more]tion of lymphocytes and macrophages in many organs, but primarily in heart and lungs. Many lesions resembled those found in autoimmune disorders, graft-vs.-host disease, or certain viral diseases. This phenotype suggests a prominent role for TGF-beta 1 in homeostatic regulation of immune cell proliferation and extravasation into tissues.[less]
Mesh Headings:
Alleles, Animals, Base Sequence, Embryo, Mammalian, Inflammation, Leukemic Infiltration, Lung, Mice, Mice, Mutant Strains, Molecular Sequence Data, Mutation, Myocardium, Phenotype, Recombinant Fusion Proteins, Syndrome, Transformation, Genetic, Transforming Growth Factor beta