These mice harbor knock-out mutations in both the Akt2 (thymoma viral proto-oncogene 2) and Ldlr (low density lipoprotein receptor), and may be useful in studies of diabetes, metabolism, hyperglycemia, and atherosclerosis.
Dr. Jan L. Breslow, Rockefeller University
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Ldlr | low density lipoprotein receptor |
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Akt2 | thymoma viral proto-oncogene 2 |
Independently, homozygous Akt2 mutant mice develop insulin resistance and diabetes, while LDLR homozygotes are predisposed to atherosclerosis. Double mutant mice that are heterozygous for the Akt2 allele and homozygous for the LDLR mutation are viable and fertile. These double mutant mice may be useful in studies of diabetes, metabolism, hyperglycemia, and atherosclerosis.
The Ldlrtm1Her mutation was made by Dr. Robert Hammer and Joachim Herz (HHMI, University of Texas Southwestern Medical Center). Briefly, a targeting vector was used to insert a neo cassette into exon 4. The vector was electroporated into 129S7/SvEvBrd-derived AB1 embryonic stem (ES) cells. Chimeric mice were bred to C57BL/6J, and the strain was made congenic on a C57BL/6J genetic background at The Jackson Laboratory (Stock No. 002207). The Akt2 mutant strain was created by Dr. Morris Birnbaum (University of Pennsylvania) by flanking exons 4-5 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. Akt2 mutant mice on a mixed (approximately 80% C57BL/6J) background were shipped to Dr. Jan Breslow at The Rockefeller University. To generate the double mutant strain, Stock No. 002207 mice were bred with Akt2 mutant mice in the laboratory of Dr. Jan Breslow at The Rockefeller University. Double mutant mice were then backcrossed to C57BL/6J for approximately 7 generations prior to arrival at The Jackson Laboratory. The donating investigators indicate that 102/10 4 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.
Allele Name | targeted mutation 1, Joachim Herz |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | LDLR-; LDLR KO; LDLr0; LDLrKO; LDLr-KO; Ldlrtm1Her |
Gene Symbol and Name | Ldlr, low density lipoprotein receptor |
Gene Synonym(s) | |
Site of Expression | Immunoblot analysis of liver membranes detected a truncated protein in homozygous mutant animals. |
Strain of Origin | 129S7/SvEvBrd-Hprt+ |
Chromosome | 9 |
General Note | When used in bone marrow transplant into Ldlrtm1Her homozygous mice, Abca1tm1Jdm Abcg1tm1Dgen homozygous cells accelerate the development of atherosclerosis. (J:130777) Phenotypic Similarity to Human Syndrome: Atherosclerosis, Susceptibility to J:29950, J:225091 in mice fed a high-cholesterol diet. |
Molecular Note | Insertion of a neomycin resistance cassette into exon 4. The authors predict that the targeted allele would encode a truncated non-functional protein that will not bind LDL, and that lacks a membrane spanning segment. Immunoblot analysis of liver membranes detected a truncated protein in homozygous mutant animals. |
Mutations Made By | Dr. Joachim Herz, Univ of Texas Southwest Med Ctr Dallas |
Allele Name | targeted mutation 1.1, Morris J Birnbaum |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Akt2-; Akt2 KO; PKBbeta- |
Gene Symbol and Name | Akt2, thymoma viral proto-oncogene 2 |
Gene Synonym(s) | |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 7 |
Molecular Note | This allele is a derivative of Akt2tm1Mbb. 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. |
Mutations Made By | Morris Birnbaum, Un of Pennsylvania Schl of Medicine |
When maintaining a live colony, these mice are bred as heterozygous for the Akt2 mutation and homozygous for the LDLR mutation.
When using the B6.129-Akt2tm1.1Mbb Ldlrtm1Her/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #006952 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Homozygous, Heterozygous or wildtype for Akt2<tm1.1Mbb>, Homozygous for Ldlr<tm1Her> |
Frozen Mouse Embryo | B6.129-Akt2<tm1.1Mbb> Ldlr<tm1Her>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.129-Akt2<tm1.1Mbb> Ldlr<tm1Her>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.129-Akt2<tm1.1Mbb> Ldlr<tm1Her>/J Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | B6.129-Akt2<tm1.1Mbb> Ldlr<tm1Her>/J Frozen Embryos | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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