These Ptpn1 (protein tyrosine phosphatase) knockout mice remain lean on a high fat diet, exhibit a decrease in adipocyte volume, increased glucose utilization and enhanced glucose tolerance. This mutant mouse strain may be useful in studies of energy regulation, diet-induced obesity and glucose metabolism.
Benjamin Neel, NYU School of Medicine
Mice that are homozygous for the targeted mutation are viable and fertile. Homozygous males exhibit decreased body weight on a standard chow diet; weight gain in females is comparable to controls. On a 55% fat diet, both males and females remain lean. Although adipocyte cell number is not decreased, adipocyte volume is significantly decreased. Basal metabolic rate and total energy expenditure are increased in male homozygotes on high fat diet. Additionally, male homozygous mice exhibit decreased leptin levels, increased insulin sensitivity as a result of increased glucose utilization in skeletal muscle and enhanced glucose tolerance.
Heterozygous males exhibit decreased body weight on a standard chow diet; however, on a 55% fat diet weight gain is similar to wild-type. Leptin levels are decreased in heterozygous males on both chow and high-fat diets.
This mutant mouse strain may be useful in studies of energy regulation, diet-induced obesity and glucose metabolism.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector containing a neomycin resistance cassette was used to replace the ATG-coding region in exon 1 and 2.3 kb of flanking sequence. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6J and then to FVB/NJ for 20 generations(see SNP note below). Upon arrival, mice were bred to FVB/NJ for at least 1 generation to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. One marker on Chromosome 7 is segregating.
|Allele Name||targeted mutation 1, Barabra B Kahn|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Ex1-; PTP-1B-; PTP1B-|
|Gene Symbol and Name||Ptpn1, protein tyrosine phosphatase, non-receptor type 1|
|Gene Synonym(s)||PTP-1B; PTP1B; Ptp|
|Strain of Origin||129S4/SvJae|
|Molecular Note||Exon 1 and surrounding sequence were replaced with a neomycin selection cassette. The absence of transcript and protein in homozygous mutant mice was verified by Northern and Western blot analyses of a variety of tissues.|
|Mutations Made By|| |
Benjamin Neel, NYU School of Medicine
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