Table 2.

Mouse models for the study of immune dysregulation in TGF-β signalopathies.

Target	Mouse model	Affected cells	Immunological phenotype	References
TGF-β1	Tgfb1-/-	Systemic effects	Increased embryonic lethality; severe autoimmunity and inflammation, reduced peripheral Treg cells, death around 3 weeks of age	(42–44)
	Tgfb1f/f	T cells	Wasting and severe colitis leading to lethality starting at 6 months of age, altered T cell activation, proliferation, and differentiation	(45)
TGF-βRI	Tgfbr1f/f	T cells	In Lck-Cre and CD4-Cre mice, lethal inflammation within 7 weeks of age; decreased thymic and splenic Treg cells	(46, 47)
TGF-βRII	Tgfbr2f/f	T cells	In CD4-Cre mice, early-onset lethal inflammation with altered T cell development and activation	(48, 49)
SMAD2	Smad2-/-	Systemic effects	Embryo lethality before E8.5	(50, 51)
	Smad2f/f	T cells	In Lck-Cre, spontaneous low grade intestinal inflammation, increased susceptibility to experimental colitis, normal T cell development in thymus and spleen, but altered T cell activation and homeostasis	(52)
SMAD3	Smad3-/-	Systemic effects	Viable, impaired TGF-β antiproliferative effect on T cells, spontaneous chronic intestinal inflammation, and immune function defects leading to death between 1 and 8 months. In LckCre-Smad2f/f, severe autoimmunity and inflammation, death within 3 to 5 weeks of age	(52–54)
ERBIN	Erbin-/-	Systemic effects	Spontaneous low grade intestinal inflammation, increased susceptibility to experimental colitis	(55)
IPO8	Ipo8-/-	Systemic effects	Not explored; evidence of increased pSMADs levels in end-stage tissues	(56)
JNK1	Jnk1-/-	Systemic effects	Hyperproliferation of T cells, decreased activation-induced cell death, altered T cell subset differentiation	(57)