These Ucp2 knock-out mice exhibit lower blood glucose levels, greater serum insulin, and aberrations in mitochondrial function. They may be useful in studies of diabetes and neurodegenerative diseases.
Bradford B. Lowell, Beth Israel Deaconess Med Cntr (Harvard)
Homozygous mice are viable and fertile and do not express full length mRNA in heart, kidney, spleen, white adipose tissue, and pancreatic islets. In splenic mitochondria, endogenous protein was undetectable. When grown under high glucose conditions, cultured pancreatic islet cells from homozygous mice have increased insulin secretion and ATP levels compared to wildtype. Homozygous mice have 18% lower blood glucose levels. Whether fasting or fed, homozygotes have approximately 3-fold greater serum insulin due to increased insulin secretion. Similarly, glucose-stimulated insulin secretion is significantly increased. High fat diet-fed mice or palmitate-treated islets maintain pancreatic glucose responsiveness in vivo and in vitro compared to wildtype. Mitochondria isolated from the dopaminergic mesencephalic nigral cells of homozygous mice have increased reactive oxygen species but lesser mitochondria number and increased sensitivity to MPTP, mimicking Parkinson's disease.
In a recent study (Endocrinology, 2009, Epub Feb 26) it was found that homozygous mutant mice exhibit increased oxidative stress as well as impaired glucose-stimulated insulin secretion, a finding that contrasts from the initial phenotype description. In the publication, it was suggested that the difference could be attributed to the earlier studies being performed on mice with a mixed B6;129S4 genetic background. These later studies, mice on a congenic B6.129S4 genetic background were used.
This mouse may be useful in studies of diabetes, glucose-dependent metabolism-secretion coupling, aerobic respiration, Parkinson's disease, epilepsy, stroke, and other neurodegenerative diseases.
A targeting vector was created by replacing exons 3-7 of the endogenous gene with a PGK-Neo expression cassette. This construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric mice were bred to C57BL/6. The resulting heterozygotes were backcrossed to C57BL/6 mice for 10 generations before arrival at the The Jackson Laboratory.
|Allele Name||targeted mutation 1, Bradford B Lowell|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Ucp2, uncoupling protein 2 (mitochondrial, proton carrier)|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A PGK-neomycin resistance cassette replaced introns 2-7 including the start codon. Northern blot analysis using a full length rat cDNA probe did not detect intact mRNA in any tissues from homozygous mutant mice. Western blot analysis did not detect protein in spleen mitochondria from homozygous mutant mice.|
|Mutations Made By|| |
Bradford Lowell, Beth Israel Deaconess Med Cntr (Harvard)
When maintaining a live colony, these mice are bred as homozygotes.
When using the UCP2 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #005934 in your Materials and Methods section.