B6.129S4(FVB)-Akt1^tm2.2Mbb/J

Stock number: 026474
Product name: Akt1^loxP
Research areas: Cell Biology Research, Diabetes and Obesity Research, Metabolism Research, Research Tools

Description

Akt1^loxP floxed mice may be useful for generating conditional mutations in applications related to the study of energy expenditure and metabolism.

Detailed description

Akt1^loxP floxed mutant mice possess loxP sites flanking exons 3-4 of the thymoma viral proto-oncogene 1 (Akt1) gene. Akt1 is a serine-threonine protein kinase that functions downstream of phosphotidylinosital 3-kinase in regulating cell survival, insulin signaling, angiogenesis and tumor formation. Mice that are homozygous for this floxed allele are viable and fertile.

When these floxed mice are bred to mice that express Cre recombinase, resulting offspring will have exons 3-4 deleted in cre-expressing tissues.
For example, when crossed to a strain with germ line Cre recombinase expression (see Stock No. 003724), resulting Akt1^-/- mice are protected from diet-induced obesity and its associated insulin resistance. They have reduced adiposity after high fat diet challenge with elevated oxygen consumption and heat production. They have significantly lower body weight than their wild-type littermates, with heterozygous KO mice displaying an intermediate phenotype.

Development

A targeting vector was designed to insert a single loxP site upstream of exon 3, and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 4 of the thymoma viral proto-oncogene 1 (Akt1) gene. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric males were bred with C57BL/6J females. Offspring were bred with mice expressing EIIa-cre to remove the floxed neo cassette. Resulting mice contained multiple gene rearrangments; intact floxed-exons 3-4, intact floxed-neo cassette, or excision of exons and the neo cassette. Progeny containing only the floxed-exons were bred to C57BL/6J mice for at least 10 generations to establish a colony of Akt1^loxP/loxP mice. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Akt1^tm2.2Mbb
Name: targeted mutation 2.2, Morris J Birnbaum
MGI accession ID: MGI:5603754
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Akt1
Marker name: thymoma viral proto-oncogene 1
Chromosome: 12
Strain of origin: 129S4/SvJae
Molecular note: A targeting vector was designed to insert a single loxP site upstream of exon 3, and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 4 of the gene. Cre-mediated recombination removed the floxed neo cassette.