Generation of mice with a conditional allele for transforming growth factor beta 1 gene

Genesis. 2009 Jun;47(6):423-31. doi: 10.1002/dvg.20516.

Abstract

Transforming growth factor beta1 (TGFbeta1) is a multifunctional growth factor involved in wound healing, tissue fibrosis, and in the pathogenesis of many syndromic diseases (e.g., Marfan syndrome, Camurati-Engelmann disease) and muscular, neurological, ophthalmic, cardiovascular and immunological disorders, and cancer. Since the generation of Tgfb1 knockout mice, there has been extraordinary progress in understanding its physiological and pathophysiological function. Here, we report the generation of a conditional knockout allele for Tgfb1 in which its exon 6 is flanked with LoxP sites. As proof of principle, we crossed these mice to LckCre transgenic mice and specifically disrupted Tgfb1 in T cells. The results indicate that T-cell-produced TGFbeta1 is required for normal in vivo regulation of peripheral T-cell activation, maintenance of T-cell homeostasis, and suppression of autoimmunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Cell Count
  • Exons / genetics*
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Targeting / methods*
  • Homeostasis / physiology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mice, Transgenic
  • Mutation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen / cytology
  • Spleen / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Thymus Gland / cytology
  • Thymus Gland / metabolism
  • Transforming Growth Factor beta1 / genetics*
  • Transforming Growth Factor beta1 / physiology

Substances

  • Transforming Growth Factor beta1