The Adult Murine Intestine is Dependent on Constitutive Laminin-γ1 Synthesis

Sci Rep. 2019 Dec 17;9(1):19303. doi: 10.1038/s41598-019-55844-x.

Abstract

Laminin-γ1 is required for early embryonic development; however, the need for laminin-γ1 synthesis in adulthood is unknown. A global and inducible mouse model of laminin-γ1 deficiency was generated to address this question. Genetic ablation of the Lamc1 gene in adult mice was rapidly lethal. Despite global Lamc1 gene deletion in tamoxifen-induced mutant mice, there was minimal change in total cardiac, pulmonary, hepatic or renal laminin protein. In contrast, laminin-γ1 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-γ1 synthesis in adult mice is dependent on a tissue-specific basal rate of laminin-γ1 turnover that results in rapid depletion of laminin-γ1 in the intestine.

Publication types

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

MeSH terms

  • Animals
  • Basement Membrane / growth & development
  • Basement Membrane / metabolism
  • Embryonic Development / genetics*
  • Female
  • Intestines / growth & development*
  • Laminin / biosynthesis
  • Laminin / genetics*
  • Liver / metabolism
  • Mice

Substances

  • Laminin
  • laminin gamma 1