B6.129S4-Cavin3^tm1Pemi/J

Stock number: 023823
Product name: Cavin-3 KO
Research areas: Cell Biology Research, Internal/Organ Research, Metabolism Research, Research Tools

Description

Cavin-3 knock-out mice exhibit cachexia and increased glycolytic metabolism. They are suitable for use in applications related to the study of ERK and Akt signaling.

Detailed description

Protein kinase C, delta binding protein, or Cavin-3, forms a complex with cavin-1 (polymerase I and transcript release factor) and caveolin to anchor caveolae to the plasma membrane at the actin cytoskeleton via myosin 1c protein. Cavin-3 is involved in ERK and AKT signaling and circadian clock regulation. These mice carry a targeted mutation in which exon 1 and most of exon 2 is replaced by a floxed NEO cassette. Homozygous mice are viable and fertile, although with a shortened lifespan. At 12 months of age homozygotes have an approximately 80% survival rate, dropping to an approximately 40% survival rate at 24 months of age. No gene product (protein) is detected by Western blot analysis of tissue (lung) or of MEFs isolated from homozygous animals. Homozygotes exhibit cachexia (40% reduction in body weight and severe lipodystrophy), hepatic steatosis, and increased glycolytic metabolism. MEFs from homozygous animals proliferate faster than MEFs from wildtype controls, exhibit Warburg metabolism, are more resistant to TNF-alpha and the MAPK/ERK Kinase (MEK) inhibitor, PD98059, and are more sensitive to the PI3K inhibitor, LY294002. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.

Development

A targeting vector containing a loxP site flanked NEO cassette was used to disrupt exon 1 and most of exon 2. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were backcrossed to C57BL/6J for 8 generations. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic 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

Symbol: Cavin3^tm1Pemi
Name: targeted mutation 1, Peter Michaely
MGI accession ID: MGI:5518819
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cavin3
Marker name: caveolae associated 3
Chromosome: 7
Strain of origin: 129S4/SvJae
Molecular note: A targeting vector containing a loxP-flanked NEO cassette was used to disrupt exon 1 and most of exon 2. No gene product (protein) is detected by Western blot analysis of MEFs isolated from homozygous animals.