These authors generated a mouse model in which the P394L mutation was knocked into the gene SQSTM1, which is the equivalent polymorphism to that commonly seen in familial Paget's disease of bone. The P394L mutant mice developed focal bone lesions with increasing age and by 12 months, 14/18 (77%) of heterozygotes and 20/21 (95%) of homozygotes had lesions, compared with 0/18 (0%) wild type littermates (p<0.001). Lesions predominantly affected the lower limbs in an asymmetric manner and were characterized by focal increases in bone turnover, with increased bone resorption and formation, disruption of normal bone architecture and accumulation of woven bone. The authors conclude that this mutation of SQSTM1 is sufficient to induce legions in mice that are very similar to those seen in humans with Paget's disease of bone.
Daroszewska A, Van't Hof RJ, Rojas JA, Layfield R, Landao-Basonga E, Rose L et al
Hum Mol Genet. 2011 Apr 21. [Epub ahead of print]