A targeting vector was designed to insert a β-galactosidase (lacZ) gene and a neomycin (neo) resistance cassette downstream of the start codon of the laminin, alpha 2 (Lama2) gene, abolishing gene function. Heterozygous dyW mice are viable, fertile and normal in size. Homozygous mice exhibit growth retardation and most die between 8 and 14 weeks of age [Moll et al. Nature September 2001 and Willmann et al. J Neuromuscul Dis. 2017]. Laminin2 (merosin) is normally expressed in striated muscle, peripheral and central nervous systems, thymus, thyroid, intestine, and testis and has been associated with merosin-deficient congenital muscular dystrophy (MCMD). Homozygous dyW mice are passive, small, and emaciated, and demonstrate partial hindleg lameness and clasping. Their muscles contain necrotic fibers with occasional areas of regeneration, and they exhibit pronounced fibrosis and increased creatine kinase (CK) activity. When heterozygous dyW mice are bred with transgenic mice expressing the mouse muscle creatine kinase (Ckm or Mck) promoter driving the expression of human LAMA2 gene, the MCMD phenotype was rescued. These transgenic dyW mice still become increasingly paralyzed with age and develop hindlimb contractures similar to nontransgenic dyW mice. These dyW mutant mice may be useful for studying merosin deficiency in MCMD and other muscular dystrophies.
