Congenital deficiency of the principal boundary lubricant in cartilage (lubricin, encoded by the gene Prg4, proteoglycan 4 (megakaryocyte stimulating factor, articular superficial zone protein)) increases joint friction and causes progressive joint failure.
These mice carry a floxed gene trap allele of the mouse Prg4 gene designed to produce membrane-anchored β-galactosidase instead of lubricin in cells where Prg4 is normally expressed. The genetrap allele does not express wildtype Prg4 mRNA, as determined by RT-PCR. Phenotypic features of the genetrap allele recapitulate those of Prg4 knockout alleles (protein deposition on cartilage by 2 months of age, increased articular joint friction, etc. - see Stock No. 025737).
Cre-mediated excision of the genetrap restores lubricin expression and the wildtype condition. Scattered areas of β-galactosidase expression may still be present in the synovium of treated mice, however, suggesting that lubricin expression may not be restored in every type B synoviocyte.
Restoring gene function prior to conception through crosses with germline-specific EIIa-cre (see Stock No. 003724) prevents cartilage damage. Tamoxifen-induced restoration of gene function (through crosses with Gt(ROSA)26SorCreERt2 (see Stock No. 008463)) at 3-weeks-of-age improves, but does not normalize, joint histology or whole joint friction. Restoring gene function in 2-month-old or 6-month-old mice has no beneficial effect.
The gene trap design additionally includes a reverse tet transactivator (rtTA) cassette.
