B6.129-Lepr^tm5Mgmj/J

Stock number: 017527
Research areas: Metabolism Research, Reproductive Biology Research, Research Tools

Description

These mice harbor a point mutation in the endogenous Lepr gene resulting in an inability of the targeted gene to activate STAT5. Reported phenotypic traits include increased weight gain and impaired estrous cycling.

Detailed description

This strain expresses a Tyr₁₀₇₇ to Phe₁₀₇₇ substitution which abolishes STAT5 activation by the mutant protein. Homozygous females exhibit increased body weight on chow diet and impaired estrous cycling, but are fertile. Homozygotes on a normal chow diet display slightly increased adipose mass and serum leptin levels. When fed a high fat diet, homozygotes are slightly heavier and have an increased food intake (approximately 5-10%) when compared to controls.

Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

Development

A targeting vector containing a Tyr₁₀₇₇ to Phe₁₀₇₇ substitution and a floxed NEO cassette was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice. The mice may have been bred to FVB, and were then backcrossed to C57BL/6J for 9 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Lepr^tm5Mgmj
Name: targeted mutation 5, Martin G Myers, Jr
MGI accession ID: MGI:5301119
Generation method: Targeted
Marker symbol: Lepr
Marker name: leptin receptor
Chromosome: 4
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: The targeting vector contained a nucleotide substitution that results in the amino acid substitution of phenyalanine for tyrosine at position 1077 (Y1077F) and a floxed NEO cassette. This mutation is predicted to abolish STAT5 activation by the mutated protein.