This NOD Alox15tm1Fun (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.
Dr. Jerry L Nadler, Eastern Virginia Medical School
Homozygous Alox15tm1Fun (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.
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 Name||targeted mutation 1, Colin D Funk|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||12/15-LO-; 12/15-LO KO; 12Lox KO; L-12/15-LOX KO; L-12LO-|
|Gene Symbol and Name||Alox15, arachidonate 15-lipoxygenase|
|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.|
|Mutations Made By|| |
Colin Funk, Queen's University