B6.129S6(SJL)-Klb^tm1.1Sakl/J

Stock number: 026883
Product name: Klb^fl
Research areas: Endocrine Deficiency Research, Internal/Organ Research, Metabolism Research, Neurobiology Research, Research Tools

Description

Klb^fl mice have loxP sites flanking exon 1 of the Klb gene. These mice are useful when studying nutrient regulation, metabolic homeostasis, and water consumption.

Detailed description

Klb^fl mice have loxP sites flanking exon 1 of the klotho beta Klb gene. KLB is a co-receptor of fibroblast growth factor 21 (FGF21), a hormone produced by the liver that signals to the brain to regulate macronutrient intake, energy homeostasis, and water consumption. KLB is also a receptor for FGF15/19, a hormone that signals from small intestine to liver to regulate bile acid homeostasis. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 1, including the translation initiation sequence, removed in the cre-expressing tissues of the offspring.

Development

The Klb^fl targeting vector was designed to insert a loxP site upstream of exon 1 and an FRT-flanked neomycin resistance cassette, followed by a second loxP site, downstream of exon 1 of the klotho beta (Klb) gene. The construct was electroporated into 129S6/SvEvTac embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred with ACTB:FLPe mice (Stock No. 003800) to remove the neo cassette. Resulting Klb^fl mice were crossed to C57BL/6J mice to remove the FLP expressing transgene, and were subsequently backcrossed to C57BL/6 mice for at least 10 generations by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Klb^tm1.1Sakl
Name: targeted mutation 1.1, Steven A Kliewer
MGI accession ID: MGI:5446140
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Klb^fl
Marker symbol: Klb
Marker name: klotho beta
Marker synonyms: AABR07015003.1; betaKlotho; BKL; Klb-ps1; RGD1308227
Chromosome: 5
Strain of origin: Not Specified
Molecular note: A loxP site was inserted upstream of exon 1. An FRT-flanked neo cassette with a 5' loxP site was inserted downstream of exon 1. Flp-mediated recombination removed the neo cassette and left exon 1 floxed.