STOCK Flnb^tm1Vshn/J

Stock number: 027233
Product name: Flnb KO
Research areas: Developmental Biology Research, Internal/Organ Research

Description

These Flnb knockout mice exhibit abnormal bone development with vertebral fusion and reduced ossification in long bones. This strain may be useful in studies of skeletal development and skeletal dysplasias such as spondylocarpaltarsal synostosis syndrome.

Detailed description

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.

Development

A targeting vector containing a NEO cassette was used to disrupt exons 3 through 5 of the targeted gene. The construct was electroporated into 129S6/SvEvTac derived iTL1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were then crossed to C57BL/6 and/or FVB. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Flnb^tm1Vshn
Name: targeted mutation 1, Volney Sheen
MGI accession ID: MGI:5620800
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Flnb
Marker name: filamin, beta
Chromosome: 14
Strain of origin: 129S6/SvEvTac
Molecular note: Exons 3-5 were replaced by a neo selection cassette causing a frame shift mutation. Western blot analysis of P7 livers confirmed graded loss of protein expression in heterozygous and homozygous mutant mice.