The majority of human skeletal dysplasias are caused by dysregulation of growth plate homeostasis. Glg1 (golgi apparatus protein 1; also known as E-selectin ligand 1) regulates growth plate homeostasis in mice by inhibiting the intracellular processing and secretion of mature transforming growth factor beta (TGFB).
These mice carry a knockout allele of Glg1 which involves a deletion of exons 13-16. Homozygous embryos and neonates (E14.5, E17.5, P3, and P7) are smaller than wildtype littermates. At birth, heterozygotes appear normal, but homozygous knockout pups are approximately 30%-50% smaller and show a higher rate of perinatal lethality.
Skeletal preparations of homozygotes show generalized shortening and thinning of all bony elements and distinctively narrow rib cages. A shortening of growth plates affecting both the proliferating zone (PZ) and the hypertrophic zone (HZ) involves decreased chondrocyte cell density and proliferation as well as increased extracellular matrix deposition. This is accompanied by increased mature TGFB2 and phosphorylated SMAD2 in the cartilage.
