Overview

Also Known As:Ankb^R1788W, B6.129(C)-Ank2^{tm3.1(R1788W)Bnt}/J

Ankb^R1788W (Ank2) knock-in mice develop a metabolic syndrome characterized by early-onset pancreatic ß 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

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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.R1788W variant, located in the unstructured C-terminal regulatory domain, is present in 0.3% of North Americans of mixed European descent and is associated with type 2 diabetes (T2D).

These knock-in mice carry the R1788W 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.

Similar to heterozygous Ank2 knockout mice (see Stock No. 027916), homozygous Ank2^R1788W mutant mice exhibit over 50% reduction in glucose-stimulated insulin secretion (normalized to total insulin content). In contrast to Ank2^R1788W mutant animals, islets isolated from homozygous Ank2^L1622I mutant animals (see Stock No. 027914) respond normally to glucose stimulation.

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.

Development

An R1788W (C to T) mutation in exon 22 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. The floxed neomycin cassette was excised though crosses with CMV-Cre mice (see Stock No. 006054). This strain was backcrossed to full C57BL/6J congenicity via speed congenic services at The Jackson Laboratory.

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

Currently there are no related genes or alleles for this strain.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

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

Mammalian Phenotype Terms by Genotype

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

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^R1788W mouse strain in a publication, please cite the originating article(s) and include JAX stock #027915 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 wildtype for Ank2<tm3.1Bnt>

Related Products and Services

Frozen Mouse Embryo	B6.129(C)-Ank2<tm3.1Bnt>/J	$2595.00
Frozen Mouse Embryo	B6.129(C)-Ank2<tm3.1Bnt>/J	$2595.00
Frozen Mouse Embryo	B6.129(C)-Ank2<tm3.1Bnt>/J	$3373.50
Frozen Mouse Embryo	B6.129(C)-Ank2<tm3.1Bnt>/J	$3373.50

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Also Known As:AnkbR1788W, B6.129(C)-Ank2tm3.1(R1788W)Bnt/J