129S4/SvJae-Fgfr2^tm6.1Sor/Mmjax

Stock number: 035806
Product name: Fgfr2^KD
Research areas: Cell Biology Research, Developmental Biology Research, Reproductive Biology Research, Sensorineural Research

Description

Fgfr2^KD (kinase dead) knock-in mice carry a K536A substitution located in the ATP binding site of the Fgfr2 (fibroblast growth factor receptor 2). The mutation is embryonic lethal in homozygotes. This strain may be useful for studying the role of Fgfr2 in development.

Detailed description

Fgfr2 (fibroblast growth factor receptor 2) encodes a tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role as a developmental regulator. These Fgfr2^KD knock-in mice carry the K536A (lysine to alanine- initially designated K517A) substitution. The mutation is located in the ATP binding site (exon 12) and phenocopies the null mutant. The mutation is embryonic lethal. E10.5 homozygous embryos lack limb buds, have an incomplete connection of the allantois to the ectoplacental cone, exhibit a dilated pericardium, posterior truncations and craniofacial defects. Mice heterozygous for Fgfr2^KD exhibit a decreased growth rate, periocular lesions (at P15-21), and a decrease in the size of the lacrimal gland as well as reduced numbers of branches and smaller lengths of tubes. Mice heterozygous for the mutation are viable (although fewer than expected are recovered at weaning) and have reduced fertility (especially females). This strain may be useful for studying the role of Fgfr2 in development.

Other Fgfr2 mutations in this series include: Fgfr2^F (MMRRC Stock No. 068000), Fgfr2^C (MMRRC Stock No. 068001), Fgfr2^PG (MMRRC Stock No. 068002), Fgfr2^CPG (MMRRC Stock No. 068003), Fgfr2^FCPG (MMRRC Stock No. 068004).

Development

The The Fgfr2^KD knock-in allele was created in the laboratory of Dr. Philippe Soriano (Icahn School at Mount Sinai). Site-directed mutagenesis was used to insert a nucleotide substitution in exon 12 of the Fgfr2 locus, altering lysine to alanine at codon 536 (K536A - GAAG to AGCT) and introducing an Alu1 site. The substitution was initially described as K517A. In addition, a FRT-flanked neomycin-resistance gene followed by a loxP site is located downstream of exon 12. The targeting vector was injected into 129S4/SvJaeSor-derived AK7 ES cells and transient Flpo-recombinase expression was used to attempt to remove the selection cassette. Removal of the neo selection cassette was unsuccessful. Chimeric males were then crossed to 129S4/SvJaeSor for germline transmission. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize 129S4/SvJaeJ (Stock No. 009104) oocytes.

Allele

Symbol: Fgfr2^tm6.1Sor
Name: targeted mutation 6.1, Philippe Soriano
MGI accession ID: MGI:6477578
Generation method: Targeted
Attributes: Not Applicable
Synonyms: Fgfr2^KD
Marker symbol: Fgfr2
Marker name: fibroblast growth factor receptor 2
Marker synonyms: BBDS; BEK; BFR-1; CD332; CEK3; CFD1; ECT1; Fgfr-2; Fgfr2b; Fgfr7; Fgfr-7; JWS; KGFR; KGFRTr; K-SAM; svs; TK14; TK25
Chromosome: 7
Strain of origin: 129S4/SvJaeSor
Molecular note: Site-directed mutagenesis was used to insert a nucleotide substitution in exon 12 of the locus, altering lysine to alanine at codon 536 (K536A - GAAG to AGCT) and introducing an Alu1 site. The substitution was initially described as K517A. In addition, a FRT-flanked neomycin-resistance gene followed by a loxP site is located downstream of exon 12. Flp-mediated recombination removed the FRT-flanked neo cassette.