B6.129P2(Cg)-Akt2^tm1.1Mbb/J

Stock number: 006966
Research areas: Diabetes and Obesity Research, Research Tools

Description

Mice homozygous for this Akt2 (thymoma viral proto-oncogene 2) mutant allele develop insulin resistance, hyperglycemia, impaired glucose tolerance, abnormal glucose uptake in muscle tissue, increased pancreatic beta-cell mass, and diabetes.

Detailed description

Mice homozygous for this Akt2 (thymoma viral proto-oncogene 2) mutant allele are viable and fertile. Homozygotes develop insulin resistance, hyperglycemia, impaired glucose tolerance, abnormal glucose uptake in muscle tissue, increased pancreatic beta-cell mass, and diabetes.

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.

Development

This mutation was created by Dr. Morris Birnbaum (University of Pennsylvania) by flanking exons 4-5 of the targeted gene with loxP sites. The targeting vector was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells, and the chimeric males were bred with C57BL/6 females. Mutant mice were then bred to cre transgenic mice to remove exons 4-5 and bred for an unknown number of generations. These mutant mice on a mixed (approximately 80% C57BL/6J) background were then shipped to Dr. Jan Breslow at The Rockefeller University. Dr. Breslow's lab crossed these mice to another mutant strain and further backcrossed to C57BL/6J for approximately 7 generations prior to arrival at The Jackson Laboratory (as Stock No. 006952). The donating investigators report that 102/104 microsatellite markers indicate C57BL/6J background; the only exceptions are D7Mit21 and D7Mit294. The Y chromosome may not have been fixed to the C57BL/6J genetic background. Upon arrival, some Stock No. 006952 mice were bred to C57BL/6J to isolate the Akt2 mutant allele; generating this single mutant congenic strain (Stock No. 006966).

Allele

Symbol: Akt2^tm1.1Mbb
Name: targeted mutation 1.1, Morris J Birnbaum
MGI accession ID: MGI:2158456
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Akt2
Marker name: thymoma viral proto-oncogene 2
Chromosome: 7
Strain of origin: 129P2/OlaHsd
Molecular note: This allele is a derivative of Akt2^tm1Mbb. Cre-mediated recombination in vivo under the control of a 6 kb 5'-flanking sequence from the Pou3f4 gene excised the floxed exons 4 and 5 in the germline. The excision of exons 4 and 5 results in a frameshift mutation that would lead to a premature termination even if the remaining exon 3 were to splice to exon 6. Exon 5 encodes the lysine residue necessary for catalytic activity. Western blot analyses using a polyclonal antibody did not detect protein in liver, muscle, and isolated adipocytes from homozygous mice.