NOD.129S2(B6)-Alox15^tm1Fun/NadlJ

Stock number: 014163
Product name: NOD. Alox15 KO
Strain synonyms: 12/15-LOX KO
Research areas: Cardiovascular Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

This NOD Alox15^tm1Fun (12/15-LO-deficient) congenic strain is useful to further study the role of Alox15 in macrophage regulation and autoimmune diabetes. Alox15 is thought to be a major candidate gene in the Idd4.1 region.

Detailed description

Homozygous Alox15^tm1Fun (12/15-LO-deficient) mutant mice are viable and fertile. Macrophages of 12/15-LO-deficient mice exhibit an absence of 12/15-LO by Rt-PCR and immunoblotting; and protein is undetectable. Diabetes incidence of mutant mice is significantly reduced compared to NOD and is reported at 2% of females and 0% of males by 7 months of age. When challenged with Glucose Tolerance Test, non-diabetic, 8-month-old, 12/15-LO-deficient females cleared glucose more efficiently than age matched, non-diabetic NOD females. Histological evaluation of the pancreas from 30 week old females shows significantly reduced insulitis and beta cell damage, compared to age-matched NOD females.

This model is useful to further study the role of Alox15 in macrophage regulation and autoimmune diabetes.

Development

Neomycin resistance cassettes were inserted into exon 3 disrupting Alox15. Properly oriented 129S2/SvPas ES cells were injected into C57BL/6 blastocysts. The germ line progeny of the chimeric male were maintained on a C57BL/6 background. B6-Alox15 mice were backcrossed to NOD followed by 4 additional crosses to NOD before intercrossing to homozygosity. It has been reported that markers D11Mit30 and D11Nds1 are of either C57BL/6 or 129 origin, while markers D11Mit177 and D11Mit245 are of NOD origin. Alox15 resides in the Idd4.1 region (McDuffie et al, 2008). In 2011, the type 1 diabetes resource received this strain at generation N5F14.

Allele

Symbol: Alox15^tm1Fun
Name: targeted mutation 1, Colin D Funk
MGI accession ID: MGI:1857428
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Alox15
Marker name: arachidonate 15-lipoxygenase
Chromosome: 11
Strain of origin: 129S2/SvPas
Molecular note: Insertion of a neomycin resistance cassette into exon 3 disrupted the Alox15 gene. Northern blot analyses of resident peritoneal macrophages and of bone marrow-derived macrophages did not detect transcript in homozygous mutant mice. Western blot analysis of resident peritoneal macrophages did not detect ALOX15 in homozygous mutant mice.