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
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Alox15 | arachidonate 15-lipoxygenase |
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 |
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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 |
Gene Synonym(s) | |
Strain of Origin | 129S2/SvPas |
Chromosome | 11 |
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 |
When using the NOD. Alox15 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #014163 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous for Alox15<tm1Fun> |
Frozen Mouse Embryo | NOD.129S2(B6)-Alox15<tm1Fun>/NadlJ | $2595.00 |
Frozen Mouse Embryo | NOD.129S2(B6)-Alox15<tm1Fun>/NadlJ | $2595.00 |
Frozen Mouse Embryo | NOD.129S2(B6)-Alox15<tm1Fun>/NadlJ | $3373.50 |
Frozen Mouse Embryo | NOD.129S2(B6)-Alox15<tm1Fun>/NadlJ | $3373.50 |
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