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Strain
C57BL/6J-Sh2b1em2Ccsu/J

Summary Data Summary
Official Name C57BL/6J-Sh2b1em2Ccsu/J
Common Name Sh2b1(?PR)
Description The Sh2b1 (SH2B adaptor protein 1) gene encodes an adaptor
protein recruited to receptor tyrosine kinases and functions
to enhance those receptors. Mutations in Sh2b1 are
associated with hyperphagia, severe obesity, insulin
resistance and neurobehavioral abnormalities. In particular,
mutations in the pleckstrin domain (PH) of Sh2b1 are
identified in the Genetics of Obesity Study (GOOS) of
individuals with severe obesity.

Sh2b1(?PR) knock-in mice carry two amino acid deletions,
P317 and R318, in the pleckstrin domain. Mice homozygous for
the mutation are viable and fertile. Beginning at 18 weeks
of age, ?PR mice exhibit increased food intake, increased
leptin levels, obesity (35-40% increase in weight on
standard chow by 20 weeks of age), hyperglycemia, impaired
glucose tolerance, and insulin resistance (males). A mild
phenotype is observed in heterozygotes (slight increase in
leptin levels, impaired glucose tolerance). Homozygous
females have reduced glucose tolerance prior to the onset of
obesity. The mutations do not alter mRNA levels, protein
levels (slight reduction in brain) or isoform selection.
However, in in vitro assays, this deletion causes the beta
isoform of SH2B1 to mislocalize from the cytoplasm and
plasma membrane to the nucleus. This strain may be useful
for studying energy balance and glucose homeostasis.
Development Status Embryonic rederivation
Creation Method knockin
TypeCount
Investigators 1
Genomics - Modifications 1
Experiments 6


Investigators
NameInstitution
Christin Carter-SuUniversity of Michigan-Ann Arbor


Genomic Information
GeneAllele 1Allele 2Protocol
Sh2b1knockinknockinNot Specified


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