Germ-free and barrier-raised TGF beta 1-deficient mice have similar inflammatory lesions

Barrier-raised transforming growth factor beta 1 (TGF beta 1)-deficient mice consistently die before 35 days of age of a severe multiorgan inflammatory disease that can affect the skeletal muscle, heart, liver, pancreas, salivary gland, lung, oesophagus and stomach. The underlying cause of this disease is not known. To determine whether abnormal responsiveness of the immune system to the presence of enteric flora plays a causative role, a colony of TGF beta 1-deficient and wild-type mice were raised in a sterile environment. Seven germ-free TGF beta 1-deficient and 5 germ-free TGF beta 1 wild-type mice were examined. Lesion development was analysed and compared with historical data on 50 barrier-raised TGF beta 1 mutant mice and 32 barrier-raised wild-type mice. All germ-free TGF beta 1-deficient mice died shortly after weaning, as do their barrier-raised counterparts. There was a significant delay in death in germ-free TGF beta 1-deficient mice compared with barrier-raised mutant mice. However, there was no difference in the type, severity or incidence of lesions between TGF beta 1 mutant mice raised under germ-free or barrier conditions. Germ-free wild-type mice had no lesions. It is concluded that microorganisms play a minimal role in disease induction in TGF beta 1-deficient mice.