title: Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death.
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 infiltration 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.
authors.affiliation: Molecular Medical Genetics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
authors.forename: A B
authors.initials: AB
authors.lastname: Kulkarni
authors.forename: C G
authors.initials: CG
authors.lastname: Huh
authors.forename: D
authors.initials: D
authors.lastname: Becker
authors.forename: A
authors.initials: A
authors.lastname: Geiser
authors.forename: M
authors.initials: M
authors.lastname: Lyght
authors.forename: K C
authors.initials: KC
authors.lastname: Flanders
authors.forename: A B
authors.initials: AB
authors.lastname: Roberts
authors.forename: M B
authors.initials: MB
authors.lastname: Sporn
authors.forename: J M
authors.initials: JM
authors.lastname: Ward
authors.forename: S
authors.initials: S
authors.lastname: Karlsson
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D004622:Embryo, Mammalian / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000401:mortality*; D017254:Leukemic Infiltration; D008168:Lung / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation; D009206:Myocardium / Q000473:pathology; D010641:Phenotype; D011993:Recombinant Fusion Proteins; D013577:Syndrome; D014170:Transformation, Genetic; D016212:Transforming Growth Factor beta / Q000172:deficiency* / Q000235:genetics
chemical_list: D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta