B6(SJL)-Efemp2^tm1.1Chu/J

Stock number: 027945
Product name: Fbln4^E57K
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research

Description

Fbln4^E57K/E57K mice contain a missense mutation in the Efemp2 gene, similar to that found in patients with autosomal recessive cutis laxa (ARCL) 1B.

Detailed description

Fbln4^E57K/E57K mice contain the amino acid mutation E57K in exon 4 of the endogenous epidermal growth factor-containing fibulin-like extracellular matrix protein 2 (Efemp2) gene. This mutation introduces a missense mutation, analogous to a mutation found in two unrelated patients with autosomal recessive cutis laxa (ARCL) 1B. Efemp2 is required for elastic fiber formation and connective tissue development. Mutations cause an autosomal recessive cutis laxa syndrome, ARCL 1B, characterized by loose skin, aortic aneurysm, arterial tortuosity, lung emphysema and skeletal abnormalities. Fbln4^E57K/E57K mice display abnormalities in multiple organ systems, including loose skin, bent forelimb, aortic aneurysm, tortuous artery and pulmonary emphysema. Processing of mature lysyl oxidase is compromised, and they have reduced levels of desmosine, an elastin specific crosslink compound. Ultrastructurally, elastic fibers and collagen fibril appear abnormal. Homozygotes are viable and fertile.

Development

A targeting construct was designed to insert a loxP- and frt-flanked neomycin (neo) resistance cassette, in reverse orientation, downstream of exon 4 of the epidermal growth factor-containing fibulin-like extracellular matrix protein 2 (Efemp2) gene. A point mutation (GAG to AAG) was introduced in exon 4, corresponding to human amino acid 57, resulting in a missense mutation, E57K, found in patients with autosomal recessive cutis laxa (ARCL) 1B. This targeting construct was electroporated into C57BL/6 embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. The resulting chimeric males were bred to C57BL/6J females. Fbln4^E57K/E57K mice were subsequently bred to B6.Cg-Tg(ACTFLPe)9205Dym/J mice (Stock No. 005703) to remove the neo cassette. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) mice for at least one generation to establish the colony.

Allele

Symbol: Efemp2^tm1.1Chu
Name: targeted mutation 1.1, Mon-Li Chu
MGI accession ID: MGI:5660409
Generation method: Targeted
Attributes: Humanized sequence
Synonyms: Fbln4^E57K
Marker symbol: Efemp2
Marker name: epidermal growth factor-containing fibulin-like extracellular matrix protein 2
Marker synonyms: 0610011K11Rik; ARCL1B; FBLN4; fibulin 4; fibulin-4; MBP1; UPH1
Chromosome: 19
Strain of origin: C57BL/6
Molecular note: The targeting construct is designed to insert a loxP- and FRT-flanked neomycin resistance cassette, in reverse orientation, downstream of exon 4. The E57K point mutation (GAG to AAG) was introduced in exon 4 resulting in a missense mutation. E57K is found in patients with autosomal recessive cutis laxa (ARCL) 1B. Flp-mediated recombination removed the FRT-flanked neo cassette.