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.
Peter Michaely, UT Southwestern Medical Center
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.
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 Name||targeted mutation 1, Peter Michaely|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, Peter Michaely; Cavin3tm1Pemi|
|Gene Symbol and Name||Cavin3, caveolae associated 3|
|Gene Synonym(s)||DIG-2; protein kinase C, delta binding protein; cavin 3; cavin-3; Prkcdbp; 3110015B12Rik; RIKEN cDNA 6330514M23 gene; RIKEN cDNA 3110015B12 gene; 6330514M23Rik; 6330514M23Rik; HSRBC; SRBC; 3110015B12Rik; Srbc; PRKCDBP; Prkcdbp|
|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.|
When maintaining a live colony, these mice can be bred as homozygotes. Homozygotes have a shortened lifespan when compared to wildtype controls (approximately 40% survival rate at 24 months of age).
When using the Cavin-3 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #023823 in your Materials and Methods section.
|Heterozygous for Prkcdbp<tm1Pemi>|
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