The Adult Murine Intestine Is Dependent On Constitutive Laminin-Gamma 1 Synthesis

Laminin-gamma 1 is required for early embryonic development; however, the need for laminin-gamma 1 synthesis in adulthood is unknown. A global and inducible mouse model of laminin-gamma 1 deficiency was generated to address this question. Genetic ablation of the Lamcl gene in adult mice was rapidly lethal. Despite global Lamcl gene deletion in tamoxifen-induced mutant mice, there was minimal change in total cardiac, pulmonary, hepatic or renal laminin protein. In contrast, laminin-gamma 1 was significantly depleted in the small intestines, which showed crypt hyperplasia and dissociation of villous epithelium from adjacent mesenchyme. We conclude that the physiologic requirement for laminin-gamma 1 synthesis in adult mice is dependent on a tissue-specific basal rate of laminin-gamma 1 turnover that results in rapid depletion of laminin-gamma 1 in the intestine.