Strain dependency of TGF?1 function during embryogenesis

Kallapur, Suhas G.; Ormsby, Ilona; Doetschman, Thomas

doi:10.1002/(sici)1098-2795(199904)52:4<341::aid-mrd2>3.0.co;2-n

Cited by 80 publications

(69 citation statements)

References 45 publications

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“…The TGF-␤1 Ϫ/Ϫ defect is also associated with a partial embryonic lethality, the penetrance of which is dependent upon genetic background (27,29). An effect of genetic background on the frequency of embryonic lethality of TGF-␤1 Ϫ/Ϫ conceptuses was observed in this study as well (Table I), with a greater frequency in the BALB/c background than in the 129/CF-1 background.…”

Section: Duration Of Survival Of Tgf-␤1 ϫ/ϫ Mice Is Modified By Genetsupporting

confidence: 68%

“…For all mating groups, this ratio was between 0 and 1, indicating partial embryonic lethality of TGF-␤1 Ϫ/Ϫ conceptuses. Genetic background is known to influence the rate of embryonic loss of TGF-␤1 Ϫ/Ϫ conceptuses (29). The data indicate that embryonic lethality of TGF-␤1 Ϫ/Ϫ conceptuses is more frequent on the inbred BALB/c background than on the outbred 129/CF-1 background.…”

Section: Screening and Monitoring Of Tgf-␤1 ϫ/ϫ Micementioning

confidence: 99%

“…These mice have been maintained as advanced intercross lines (28), to maintain a heterogeneous genetic background. The genetic background of these mice is a hybrid of 129/SvPas and CF-1 (Charles River Breeding Laboratories, Wilmington, MA) genomic material (29). BALB/c background IFN-␥ Ϫ/Ϫ mice (30) were purchased from The Jackson Laboratory (sixth backcross generation, according to the supplier; calculated BALB/c genomic material ϭ 99.2%).…”

Section: Generation Of Breeder Micementioning

confidence: 99%

“…All three PCR involve primers that are specific for, and that flank the neo interruption of, the gene of interest. The TGF-␤1 PCR incorporates a third, additional primer from the neomycin cassette, which improves the efficiency and reliability of the reaction and does not affect the specificity (29). For all three PCR, a faster migrating band reflects the wild-type allele, while a slower migrating band reflects the interrupted allele.…”

Section: Genotypingmentioning

confidence: 99%

“…An effect of genetic background on the frequency of embryonic lethality of TGF-␤1 Ϫ/Ϫ conceptuses was observed in this study as well (Table I), with a greater frequency in the BALB/c background than in the 129/CF-1 background. The mechanism(s) of embryonic lethality is obscure, but appears to be due to developmental defects and unrelated to immune or inflammatory responses (29,33) and is not considered further in this study.…”

Section: Duration Of Survival Of Tgf-␤1 ϫ/ϫ Mice Is Modified By Genetmentioning

confidence: 99%

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Genetic Regulation of Autoimmune Disease: BALB/c Background TGF-β1-Deficient Mice Develop Necroinflammatory IFN-γ-Dependent Hepatitis

Gorham¹,

Lin²,

Sung³

et al. 2001

The Journal of Immunology

114

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Autoimmune hepatitis (AIH) in humans arises spontaneously in genetically susceptible individuals and is associated with the presence of Th1 cells in the liver. The understanding of AIH has advanced more slowly than that of other organ-specific autoimmune diseases, however, largely because of the lack of an appropriate animal model. We now describe a new mouse model characterized by spontaneous development of necroinflammatory hepatitis that is restricted by genetic background. Mice deficient in the immunomodulatory cytokine TGF-β1 were extensively back-bred to the BALB/c background. The BALB/c background dramatically modified the phenotype of TGF-β1−/− mice: specifically, BALB/c-TGF-β1−/− mice developed a lethal necroinflammatory hepatitis that was not observed in TGF-β1−/− mice on a different genetic background. BALB/c background TGF-β1−/− livers contained large numbers of activated CD4+ T cells that produced large quantities of IFN-γ, but little IL-4, identifying them as Th1 cells. BALB/c background TGF-β1−/−/IFN-γ−/− double knockout mice, generated by cross-breeding, did not develop necroinflammatory hepatitis, demonstrating that IFN-γ is mechanistically required for its pathogenesis. This represents the first murine model of hepatitis that develops spontaneously, is restricted by genetic background, and is dependent upon the Th1 cytokine IFN-γ, and that thus recapitulates these important aspects of AIH.

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Section: Duration Of Survival Of Tgf-␤1 ϫ/ϫ Mice Is Modified By Genetsupporting

confidence: 68%

Section: Screening and Monitoring Of Tgf-␤1 ϫ/ϫ Micementioning

confidence: 99%

Section: Generation Of Breeder Micementioning

confidence: 99%

Section: Genotypingmentioning

confidence: 99%

Section: Duration Of Survival Of Tgf-␤1 ϫ/ϫ Mice Is Modified By Genetmentioning

confidence: 99%

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