Filamin beta stabilizes 3D actin filament networks, connecting the cell membrane to the actin cytoskeleton. It has roles in regulating intracellular signaling, cell motility, organ development, tumor growth and metastasis. Mutations of FLNB are the cause of a group of human skeletal dysplasia disorders including spondylocarpotarsal syndrome, boomerang dysplasia, Larsen syndrome and atelosteogenesis I and III. These mice carry a knock out mutation for the Flnb gene in which exons 3 through 5 are replaced by a NEO cassette. Mice that are homozygous for the targeted mutation have a high death rate around the time of birth. Adult male homozygotes are fertile but exhibit mating problems due to deformity. Some surviving homozygous females exhibit dystocia. Heterozygotes are viable and fertile.
No gene product (protein) is detected by Western blot analysis of liver from 7 day old homozygotes and growth plate of the radius from E16.5 homozygotes. Surviving male homozygotes exhibit a small body size, lower body weight, shortened distal limbs, rib and vertebrae fusion, abnormal spinal curvatures, and dysmorphic facial/calvarial bones. Female homozygotes display a small body size, vertebral fusions and joint laxity. Homozygotes have a delay in endochondral bone development, reduced bone ossification, and disrupted extracellular matrix organization. Chondrocyte differentiation in long bones is delayed while proliferation is disrupted.
