This diabetes resistant congenic NOD.Itgal deficient mutant may be useful to further study the role of leukocyte intergrins in inflammatory disease models, specifically Type 1 Diabetes.
Dr. Christopher G. Kevil, LSU Health Sciences Center
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. NOD females homozygous for the Itgal mutation (commonly referred to as LFA1 or CD11a) remain normoglycemic to 34 weeks of age. Histological evaluation indicated the pancreatic islets were mostly normal, but some lymphocytic infiltrates were observed. Cd18, Cd11a and Cd49 expression are significantly reduced in splenic CD3 T-cells. Adoptive transfer experiments utilizing NOD-Rag1 mutant mice that received splenocytes from NOD-Itgal mutant mice did not become diabetic and no insulitis was observed. However, there were more leukocytes and CD3+ T-cells found than in control transfer experiments.
NODShiLtJ mice carrying the Itgal mutation may be useful to further study the role of leukocyte intergrins in T-cell activation leading to insulitis and Type 1Diabetes.
A targeting vector containing neomycin resistance gene driven by the mouse RNA polymerase II promoter was used to disrupt a 2.1 kb region containing exons 1 and 2. The construct was electroporated into 129S7/SvEvBrd-Hprtb-m2 derived AB2.1 embryonic stem (ES) cells. The LFA-1 mutant mice (also called Cd11a or Itgal mutant mice) were maintained on a C57BL/6 background prior to 8 backcross generations to NOD/ShiLtJ. In 2011, the T1Dr received this strain at generation N8F14.
|Allele Name||targeted mutation 1, Christie M Ballantyne|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Cd11a(-); CD11alpha KO; LFA-1-|
|Gene Symbol and Name||Itgal, integrin alpha L|
|Strain of Origin||129S7/SvEvBrd-Hprtb-m2|
|Molecular Note||Exons 1 and 2 were replaced with a neomycin selection casssette inserted by homologous recombination.|
|Mutations Made By|| |
Huaizhu Wu, Baylor College of Medicine
While maintaining a live colony this strain was mated homozygous x homozygous.
When using the NOD-Cd11a mouse strain in a publication, please cite the originating article(s) and include JAX stock #016898 in your Materials and Methods section.