Mice homozygous for the LeprS1138 mutant allele (or s/s mice) have a Tyr->Ser replacement at amino acid residue 1138 of the leptin receptor long form (LRb)-specific exon 18b that specifically disrupts LRb-STAT3 transcription factor signaling, and may be useful for studying LRb-STAT3 signaling in the physiological and metabolic function of leptin; specifically body energy homeostasis and neuroendocrine function, glucose homeostasis, melanocortin production, neuropeptide Y, obesity, diabetes, fertility and growth.
Martin G Myers, University of Michigan Medical School
Mice homozygous for the LeprS1138 mutant allele (or s/s mice) are viable and partially fertile with a Tyr->Ser replacement at amino acid residue 1138 of the leptin receptor long form (LRb)-specific exon 18b. The mutation specifically disrupts LRb-STAT3 transcription factor signaling. The mutant protein, LRbS1138, is expressed normally on the cell surface and mediates other leptin signals normally, but fails to activate STAT3. Similar to homozygous db/db mice (which are devoid of all leptin signaling), homozygous s/s mice display hyperphagia, decreased energy expenditure, and decreased thyroid function resulting in profound obesity and dramatically increased serum leptin levels compared to wild-type. Unlike db/db mice, however, s/s mice are fertile and long bodied, have improved glucose tolerance (less hyperglycemic), are not protected from intimal hyperplasia following vessel injury, and do not exhibit elevated hypothalamic expression of neuropeptide Y (NPY). Homozygous LeprS1138 mutant mice may be useful for studying LRb-STAT3 signaling in the physiological and metabolic function of leptin; specifically body energy homeostasis and neuroendocrine function, glucose homeostasis, melanocortin production, neuropeptide Y, obesity, diabetes, fertility and growth.
A targeting vector was designed to replace the tyrosine residue at amino acid 1138 of the leptin receptor long form (LRb)-specific exon 18b of the targeted gene with a serine residue (and also insert a neo cassette downstream of exon 18b). The donating investigator reports that the construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells and the resulting chimeric animals were bred with C57BL/6 (Taconic) mice to generate LRbS1138 mutant mice. These mice were then backcrossed at least 15 generations to C57BL/6 (Taconic) prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred with C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Martin G Myers, Jr|
|Allele Synonym(s)||Leprtm1Mgmj; targeted mutation 1, Martin G Myers, Jr|
|Gene Symbol and Name||Lepr, leptin receptor|
|Gene Synonym(s)||diabetes; OB-R; OB-RGRP; obese-like; obl; OBR; CD295; LEP-R; Leprb; LEPRD; LEPROT; obl; Modb1; leptin receptor gene-related protein; obese-like; db; Fa; Obr|
|Promoter||Lepr, leptin receptor, mouse, laboratory|
|Strain of Origin||129/Sv|
|Molecular Note||Tyrosine 1138 of exon 18b was replaced with a serine residue (Y1138S) and a neomycin resistance cassette was inserted into the downstream intron via homologous recombination. The Y1138S amino acid substitution specifically disrupts the leptin receptor long form (LRb)-STAT3 signal. Expression of the knock-in allele in mutant animals was confirmed by semi-quantitative RT-PCR analysis of hypothalamus RNA.|
|Mutations Made By|| |
Martin Myers, University of Michigan Medical School
When maintaining a live colony, heterozygous mice may be bred together. The donating investigator reports that homozygous mice are partially fertile.
When using the B6.129-Leprtm1Mgmj/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008518 in your Materials and Methods section.
|Heterozygous or Wild-type for Lepr<tm1Mgmj>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
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