TGF-β1L-β3/L-β3 mice contain an HA-tagged transforming growth factor, beta 3 (Tgfb3) cDNA, and a frt-flanked neo cassette, expressed under control of the transforming growth factor, beta 1 (Tgfb1) promoter/enhancer sequences. TGFB isoforms are important cytokines that influence cell growth, cell differentiation, apoptosis, and cellular homeostasis. Each isoform contains a latency associated peptide (LAP) domain, required for localization and activation, and a receptor binding ligand, required for cell signaling. Each LAP sequences only shares 40% sequence homology between isoforms, while the ligands share 80% homology and all contain nine conserved cysteines. All three TGF-β proteins have distinct cell-specific expression patterns that reflect the differences in the promoters located within each homologue's gene. In these TGF-β1L-β3/L-β3 mice, the TGF-β1 LAP is maintained for localization and activation but cell signaling occurs through the TGF-β3 ligand. These mice do not exhibit the embryonic lethality, vasculogenesis defects, or autoimmunity associated with TGF-β1 deficiency. These TGF-β1L-β3/L-β3 mice have a shortened lifespan and display tooth and bone mineralization defects. These mice display an improved metabolic phenotype with reduced body weight gain and enhanced glucose tolerance, by induction of beneficial changes to the white adipose tissue compartment. These mice also exhibit no defects in palate development. Homozygotes are viable and fertile, with a median survival of 30.5 weeks.
