B6.129S1-Timp3^tm1Hest/J

Stock number: 036854
Product name: Timp3^-
Research areas: Sensorineural Research

Description

Timp3^- mice carry a targeted knock-out of the mouse Timp3 (tissue inhibitor of metalloproteinase 3) gene that involves the disruption of exon 3 with a neomycin cassette. This strain has been useful in studies of Sorsby fundus dystrophy (SFD), a rare, late-onset macular dystrophy.

Detailed description

Sorsby fundus dystrophy (SFD) is a rare, late-onset macular dystrophy caused by mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) gene. SFD is manifested by symptoms of night blindness or sudden loss of visual acuity due to choroidal neovascularization.

Timp3^- mice carry a targeted knock-out of the mouse Timp3 (tissue inhibitor of metalloproteinase 3) gene that involves the disruption of exon 3 with a neomycin cassette. The absence of protein product was confirmed by western blot analysis on primary fibroblast extracts from homozygotes.

Homozygotes show distinct choroidal, but not retinal phenotype, characterized by prominently enlarged choroidal blood vessels. Evidence supports the hypothesized role of TIMP3 in regulation of choroidal vascularization of the retina.

Development

A PGK-neomycin cassette was inserted into exon 3 of the mouse Timp3 gene via homologous recombination in 129S1/Sv-Oca2⁺Tyr⁺Kitl ⁺-derived CJ7 embryonic stem (ES) cells. This mutation leads to a frame shift and the introduction of a premature stop codon. Resultant mice were backcrossed to C57BL/6J for 19 generations by the donating laboratory.

Upon arrival at The Jackson Laboratory, sperm was cryopreserved. Cryorecovery/live colony development will involve C57BL/6J (Stock No. 000664).

Allele

Symbol: Timp3^tm1Hest
Name: targeted mutation 1, Heidi Stohr
MGI accession ID: MGI:3797605
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Timp3
Marker name: tissue inhibitor of metalloproteinase 3
Marker synonyms: HSMRK222; K222; K222TA2; SFD; Timp-3
Chromosome: 10
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: A neo cassette was inserted into exon 3 leading to a frame shift and the introduction of a premature stop codon. The absence of protein product was confirmed by western blot analysis on primary fibroblast extracts.