AnkbL1622I/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.
Vann Bennett, Duke University Medical Center
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Humanized sequence) | Ank2 | ankyrin 2, brain |
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 Ank2R1788W/R1788W mutant animals (see Stock No. 027915), islets isolated from Ank2L1622I/L1622I mutant animals respond normally to glucose stimulation. Homozygous Ank2R1788W 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 Ank2R1788W and Ank2L1622I 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 Ank2R1788W and Ank2L1622I knock-in mice, respectively. Heterozygotes demonstrate 1.8- and 1.4-fold increases, respectively.
Both 3-month-old and 10-month-old Ank2R1788W and Ank2L1622I 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 Ank2R1788W and Ank2L1622I homozygous mutant mice exhibit
significant adipocyte hypertrophy (54% increase in adipocyte diameter in Ank2R1788W and 38% in Ank2L1622I 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 Ank2L1622I mutation have a cardiac phenotype.
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.
Allele Name | ankyrin 2, brain; targeted mutation 2, Vann Bennett |
---|---|
Allele Type | Targeted (Humanized sequence) |
Allele Synonym(s) | Ank2L1622I |
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. |
Heterozygotes and homozygotes are viable and fertile.
When using the AnkbL1622I mouse strain in a publication, please cite the originating article(s) and include JAX stock #027914 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Ank2<tm2Bnt> |
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 |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
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.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.