Overview

Also Known As:Ankb^L1622I, B6.129(C)-Ank2^{tm2.1(L1622I)Bnt/J}

Ankb^{L1622I/L1622I} (Ank2) knock-in mice develop a metabolic syndrome characterized by early-onset pancreatic β cell dysfunction and age- or diet-dependent increases in adiposity and insulin resistance. Tissue-specific ANK2 deficiency is also observed.

Donating Investigator

Vann Bennett, Duke University Medical Center

Genetic overview

Genetic Background	Generation

Ank2^tm2Bnt

Allele Type	Gene Symbol	Gene Name
Targeted (Humanized sequence)	Ank2	ankyrin 2, brain

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Research Applications

Diabetes and Obesity Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Ankyrin-B (Ank2; AnkB) is a member of the ankyrin family of membrane adaptors that contributes to the assembly of diverse specialized plasma membrane domains. In humans, the p.L1622I variant, located in the unstructured C-terminal regulatory domain, is the most common ANK2 mutation in African Americans at over 7%, with a presence of less than 0.1% of individuals of mixed European decent. In humans, the mutation is involved with the setting of hereditary cardiac arrhythmia.

These knock-in mice carry the L1622I mutation in the Ank2 gene. Homozygotes develop a metabolic syndrome characterized by early-onset pancreatic β cell dysfunction and age- or diet-dependent increases in adiposity and insulin resistance. Tissue-specific ANK2 deficiency is also observed.

Homozygous mice are born at the expected Mendelian ratios and exhibit no differences in mRNA levels, as assessed by qPCR. Protein levels in homozygotes, however, are reduced significantly in a subset of tissues, including fat, liver, skeletal muscle, pancreatic β cells, and heart. Primary mouse embryonic fibroblast (MEF) cultures also show reduced protein expression. No change in protein expression is detected in the brain.

In contrast to Ank2^{R1788W/R1788W} mutant animals (see Stock No. 027915), islets isolated from Ank2^{L1622I/L1622I} mutant animals respond normally to glucose stimulation. Homozygous Ank2^R1788W mutant mice exhibit over 50% reduction in glucose-stimulated insulin secretion (normalized to total insulin content).

While fasting serum glucose levels are unaltered in both Ank2^R1788W and Ank2^L1622I homozygous mice, oral administration of glucose (2 g/kg body weight) during an oral glucose tolerance test leads to both an increased level of blood glucose at 30 minutes as well as a delay in glucose clearance. The areas under the blood glucose response curves are significantly increased by 2- and 1.7 fold in homozygous Ank2^R1788W and Ank2^L1622I knock-in mice, respectively. Heterozygotes demonstrate 1.8- and 1.4-fold increases, respectively.

Both 3-month-old and 10-month-old Ank2^R1788W and Ank2^L1622I homozygous mice show overall similar average rates of food intake, energy source utilization, and activity compared with littermate controls during both light and dark cycles.

Both Ank2^R1788W and Ank2^L1622I homozygous mutant mice exhibit
significant adipocyte hypertrophy (54% increase in adipocyte diameter in Ank2^R1788W and 38% in Ank2^L1622I mice) which is accompanied by elevated levels of circulating nonesterified fatty acids. The increase in body fat is more prominent than the overall changes in total body weight.

It has not been determined whether mice carrying the Ank2^L1622I mutation have a cardiac phenotype.

Development

An L1622I (CTG to ATC) mutation in exon 19 and loxP-flanked neomycin cassette were knocked into the mouse Ank2 gene through homologous recombination in 129-derived embryonic stem cells. Resultant chimeric mice were bred with C57BL/6J animals. Although it was reported that the floxed neomycin cassette was excised though crosses with CMV-Cre mice (see Stock No. 006054), the neomycin cassette, segregating with the L1622I mutation, is still present.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Three of the 27 markers throughout the genome were segregating, suggesting an incomplete backcross.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Lorenzo DN; Healy JA; Hostettler J; Davis J; Yang J; Wang C; Hohmeier HE; Zhang M; Bennett V. 2015. Ankyrin-B metabolic syndrome combines age-dependent adiposity with pancreatic beta cell insufficiency. J Clin Invest 125(8):3087-3102PubMed: 26168218 MGI: J:222913

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Genetics

Ank2^tm2Bnt

Allele Symbol: Ank2^tm2Bnt

Allele Name	ankyrin 2, brain; targeted mutation 2, Vann Bennett
Allele Type	Targeted (Humanized sequence)
Allele Synonym(s)	Ank2^L1622I
Gene Symbol and Name	Ank2, ankyrin 2, brain
Gene Synonym(s)
Strain of Origin	129
Chromosome	3
Molecular Note	An L1622I (CTG to ATC) mutation in exon 19 and loxP-flanked neomycin cassette were knocked into the gene. In humans, the mutation is involved with the setting of hereditary cardiac arrhythmia.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Diabetes and Obesity Research
- Obesity With Diabetes
  - diet-induced
  - adult onset
- Insulin Resistance
  - diet-induced
  - adult onset
- Type 2 Diabetes (NIDDM)

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Ank2^tm2Bnt/Ank2^tm2Bnt
involves: 129

mammalian phenotype

no phenotypic analysis
- Normal - the version of this allele that does not contain the neomycin selection cassette, Ank2^tm2.1Bnt, has been analyzed

References

Lorenzo DN; Healy JA; Hostettler J; Davis J; Yang J; Wang C; Hohmeier HE; Zhang M; Bennett V. 2015. Ankyrin-B metabolic syndrome combines age-dependent adiposity with pancreatic beta cell insufficiency. J Clin Invest 125(8):3087-3102PubMed: 26168218 MGI: J:222913

Additional - Ank2^tm2Bnt related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Sanger sequencing:Ank2
- Genotyping resources and troubleshooting
Breeding Considerations

Heterozygotes and homozygotes are viable and fertile.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Heterozygote
Citation
When using the Ankb^L1622I mouse strain in a publication, please cite the originating article(s) and include JAX stock #027914 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 for Ank2<tm2Bnt>

Related Products and Services

Frozen Mouse Embryo	STOCK Ank2<tm2Bnt>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	STOCK Ank2<tm2Bnt>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	STOCK Ank2<tm2Bnt>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	STOCK Ank2<tm2Bnt>/J Frozen Embryo	$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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Also Known As:AnkbL1622I, B6.129(C)-Ank2tm2.1(L1622I)Bnt/J

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Ank2tm2Bnt

Allele Symbol: Ank2tm2Bnt

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Ank2tm2Bnt/Ank2tm2Bntinvolves: 129

mammalian phenotype

References

Additional - Ank2tm2Bnt related

Genotyping Protocols

Breeding Considerations

Mating System

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

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As:Ankb^L1622I, B6.129(C)-Ank2^{tm2.1(L1622I)Bnt/J}

Ank2^tm2Bnt

Allele Symbol: Ank2^tm2Bnt

Genotype: Ank2^tm2Bnt/Ank2^tm2Bnt
involves: 129

Additional - Ank2^tm2Bnt related