Deficiency of perlecan increases the risk of osteoporosis in patients with Schwartz-Jampel Syndrome (SJS) and attenuates loading-induced bone formation in perlecan deficient mice (Hypo).
As five of the seven missense mutations in SJS affect domain III of perlecan, domain III is likely to be essential for secretion of perlecan into the extracellular space.
Altogether, our data shed light on perlecan function by revealing critical roles in Schwann cell physiology and suggest that PNH in SJS originates distally from synergistic actions of peripheral nerve and neuromuscular junction changes.
We used homologous recombination to generate a knock-in mouse strain with one missense substitution, corresponding to a human familial SJS mutation (p.C1532Y), in the perlecan gene.
These studies question the C1532Y mutation as the sole causative factor of SJS in the human family harboring this alteration and imply that transcriptional changes leading to perlecan reduction may represent the disease mechanism for SJS.
These studies question the C1532Y mutation as the sole causative factor of SJS in the human family harboring this alteration and imply that transcriptional changes leading to perlecan reduction may represent the disease mechanism for SJS.
These findings suggest that perlecan has an important role in neuromuscular function and cartilage formation, and they define the molecular basis involved in the difference in the phenotypic severity between DDSH and SJS.
This resistance to NDMR may result from a lower acetylcholine degradation rate suggested as being the consequence of mutation of the gene encoding perlecan (HSPG2) in SJS.