These mice contain loxP flanked transcription blocker (loxTB) sequence between exons 16 and 17 of the leptin receptor (Lepr) gene, abolishing transcription of the exons downstream of the loxTB. Leptin is an adipose-derived hormone that acts to regulate food intake, energy expenditure, and body weight. LeprloxTB mice, lacking the long (B) isoform of the leptin receptor, are obese, hyperglycemic, and hyperinsulinemic, and have reduced energy expenditure. Mice that are heterozygous for the targeted mutation are viable and fertile, while homozygous mice are infertile. When these mutant mice are bred to mice that express Cre recombinase, the resulting offspring will have the loxTB removed and Lepr expression will be restored in cre expressing cells.
For example, when bred to STOCK Tg(Pomc1-cre)16Lowl/J mice (Stock No. 005965) expressing Cre-recombinase in proopiomelanocortin (POMC) neurons, the resulting offspring have normal glucose and glucagon levels. They have moderately restored energy expenditure and body weight, with no reduction on food intake.
A targeting vector was used to insert a loxP flanked transcription blocker (loxTB), containing multiple polyadenylation signals and a neomycin resistance cassette (neo), between exons 16 and 17 of the leptin receptor (Lepr) gene. The construct was electroporated into 129X1-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into C57BL/6Jrecipient blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice and were subsequently crossed to FVB. These LeprloxTB mice were maintained on a mixed background. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Allele Name||targeted mutation 1, Joel K Elmquist|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Lepr, leptin receptor|
|Strain of Origin||129X1/SvJ|
|Molecular Note||A floxed transcription blocker was inserted into intron 16.|
|Mutations Made By|| |
Joel Elmquist, UT Southwestern Med Center at Dallas
When maintaining a live colony heterozygous mice may be bred together. Homozygous mice are infertile.
When using the LeprloxTB mouse strain in a publication, please cite the originating article(s) and include JAX stock #018989 in your Materials and Methods section.
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