Overview

Also Known As:Akita LDLR KO

These double mutant mice carry the Akita mutation, characterized by early-onset NIDDM, and an Ldlr knock-out, characterized by increased plasma cholesterol levels.

Donating Investigator

Dr. Jan L. Breslow, Rockefeller University

Genetic overview

Genetic Background	Generation

Ins2^Akita

Allele Type	Gene Symbol	Gene Name
Spontaneous	Ins2	insulin II

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ldlr	low density lipoprotein receptor

Research Applications

Metabolism Research
Diabetes and Obesity Research
Cell Biology Research
Cardiovascular Research
Mouse/Human Gene Homologs
Endocrine Deficiency Research
Research Tools

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the Akita spontaneous mutation die postnatally, typically by 12 weeks of age. Independently, heterozygous Akita mutant mice are a model of insulin dependent diabetes mellitus (IDDM) with severe hyperglycemia (see the datasheet for Stock No. 003548 for additional information). LDLR-null homozygotes have elevated serum cholesterol levels (200-400 mg/dl) which can escalate to very high levels (> 2000 mg/dl) when the mice are fed a high fat diet. LDLR-deficient mice also are predisposed to develop atherosclerosis. These double mutant mice may be useful in studies of diabetes, metabolism, hyperglycemia, atherosclerosis, hypercholesterolemia, and diabetes-related macrovascular complications.

Development

The Ldlr^tm1Her 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 Akita spontaneous mutation in the insulin II gene (originally called Mody4) was identified on the C57BL/6NScl genetic background by Dr. Akio Koizumi (The Akita University School of Medicine). These mice were shipped to The Jackson Laboratory and then backcrossed on to the C57BL/6J genetic background (Stock No. 003548). To generate the double mutant strain, Stock No. 002207 mice were bred with Stock No. 003548 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 103/104 microsatellite markers indicate C57BL/6J background. The single exception is D7Mit81.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

Ins2^Akita

Allele Symbol: Ins2^Akita

Allele Name	Akita
Allele Type	Spontaneous
Allele Synonym(s)	Akita; Akita^Ins2; Ins2^C96Y; Ins2^Mody; Mody; Mody4
Gene Symbol and Name	Ins2, insulin II
Gene Synonym(s)
Strain of Origin	C57BL/6NSlc
Chromosome	7
Molecular Note	In the mutant allele a transition from G-to-A at coding nucleotide 287 disrupts an Fnu4HI site in exon 3. This mutation changed the seventh amino acid in the A chain of mature insulin, Cys96 (TGC), to Tyr (TAC) (p.C96Y). The authors predict that the transition would disrupt a disulfide bond between the A and the B chains and would likely induce a major conformational change in insulin 2 molecules. RT-PCR studies suggest that both normal and mutant Ins2 alleles are transcribed similarly in pancreatic islets of heterozygous mice, although immunofluorescence and immunoblot analyses of heterozygous islets detected reduced levels of insulin and proinsulin.

Ldlr^tm1Her

Allele Symbol: Ldlr^tm1Her

Allele Name	targeted mutation 1, Joachim Herz
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 Ldlr^tm1Her homozygous mice, Abca1^tm1Jdm Abcg1^tm1Dgen 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

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

diabetic angiopathy

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Ldlr^tm1Her related

Metabolism Research
- Lipid Metabolism
Cardiovascular Research
- Atherosclerosis
- Hypercholesterolemia
Mouse/Human Gene Homologs
- hypercholesterolemia, familial

Genotype: Ins2^Akita related

Diabetes and Obesity Research
- Impaired Insulin Processing
- Islet Transplantation Studies
- Hyperglycemia
- Hypoinsulinemia
- Insulin Receptors and Growth Factors
- Type 1 Diabetes (IDDM)
  - MODY, mature onset diabetes of the young
Cell Biology Research
- Protein Processing
Endocrine Deficiency Research
- Pancreas Defects

Diabetes and Obesity Research
- Type 1 Diabetes (IDDM)
- Hypoinsulinemia
- Hyperglycemia
Research Tools
- Metabolism Research
- Cardiovascular Research
- Diabetes and Obesity Research
Cardiovascular Research
- Other
  - altered fat metabolism
- Atherosclerosis
- Hypercholesterolemia
Metabolism Research
- Lipid Metabolism

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Ins2^Akita/Ins2^Akita Ldlr^tm1Her/Ldlr^tm1Her
B6.Cg-Ins2 Ldlr

cardiovascular system phenotype

increased susceptibility to atherosclerosis
- accelerated in mice fed a high-fat diet compared with similarly treated Ldlr^tm1Her homozygotes

mortality/aging

premature death
- compared with Ldlr^tm1Her homozygotes

growth/size/body region phenotype

decreased body weight
- in male, but not female, mice at 20 weeks of age compared with Ldlr^tm1Her homozygotes

homeostasis/metabolism phenotype

decreased circulating insulin level
- in fasting mice compared with Ldlr^tm1Her homozygotes

hyperglycemia
- severe compared with Ldlr^tm1Her homozygotes

impaired glucose tolerance
- compared with Ldlr^tm1Her homozygotes

increased circulating cholesterol level
- in fasting mice compared with Ldlr^tm1Her homozygotes

increased circulating HDL cholesterol level
- in female mice compared with Ldlr^tm1Her homozygotes

increased circulating LDL cholesterol level
- 2-fold in male mice and 24% in female mice compared with Ldlr^tm1Her homozygotes

increased circulating triglyceride level
- in fasting mice compared with Ldlr^tm1Her homozygotes

increased circulating VLDL cholesterol level
- 7-fold in male mice and 1.8-fold in female mice compared with Ldlr^tm1Her homozygotes

References

Additional References

Ishibashi S; Brown MS; Goldstein JL; Gerard RD; Hammer RE; Herz J. 1993. Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery [see comments] J Clin Invest 92(2):883-93PubMed: 8349823 MGI: J:37394
Yoshioka M; Kayo T; Ikeda T; Koizumi A. 1997. A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice. Diabetes 46(5):887-94PubMed: 9133560 MGI: J:40063

Additional - Ins2^Akita related

Additional - Ldlr^tm1Her related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Restriction Enzyme Digest:Ins2
- Pyrosequencing:Ins2
- End Point Analysis:Ins2
- Standard PCR:Ldlr-alternate 1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice are bred as heterozygous for the Akita mutation and homozygous for the LDLR mutation.
- Additional Breeding and Husbandry Support
Citation
When using the Akita LDLR KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #006580 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Homozygous for Ldlr<tm1Her>, Heterozygous or Wild type for Ins2<Akita>

Related Products and Services

Frozen Mouse Embryo	B6.Cg-Ins2<Akita> Ldlr<tm1Her>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.Cg-Ins2<Akita> Ldlr<tm1Her>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.Cg-Ins2<Akita> Ldlr<tm1Her>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6.Cg-Ins2<Akita> Ldlr<tm1Her>/J Frozen Embryos	$3373.50

Payment Terms and Conditions

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The Jackson Laboratory's Genotype Promise

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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General Terms and Conditions

Questions about Terms of Use

Licensing Information

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JAX® Mice, Products & Services Conditions of Use

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Also Known As:Akita LDLR KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Ins2Akita

Allele Symbol: Ins2Akita

Ldlrtm1Her

Allele Symbol: Ldlrtm1Her

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Ldlrtm1Her related

Genotype: Ins2Akita related

Mammalian Phenotype Terms by Genotype

Genotype: Ins2Akita/Ins2Akita Ldlrtm1Her/Ldlrtm1HerB6.Cg-Ins2 Ldlr

cardiovascular system phenotype

mortality/aging

growth/size/body region phenotype

homeostasis/metabolism phenotype

References

Additional References

Additional - Ins2Akita related

Additional - Ldlrtm1Her related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Ins2^Akita

Allele Symbol: Ins2^Akita

Ldlr^tm1Her

Allele Symbol: Ldlr^tm1Her

Genotype: Ldlr^tm1Her related

Genotype: Ins2^Akita related

Genotype: Ins2^Akita/Ins2^Akita Ldlr^tm1Her/Ldlr^tm1Her
B6.Cg-Ins2 Ldlr

Additional - Ins2^Akita related

Additional - Ldlr^tm1Her related