No membrane bound ICAM-1 is detectable in NOD.129S4(B6)-Icam1tm1Jcgr/SmtnJ homozygous mice. NOD mice homozygous for the Icam1tm1Jcgr mutation are diabetes resistant. Histological exam shows no or mild peri-insular infiltration at 330-410 days of age, while 64% of their wild-type cohorts and 44% of the heterozygote animals become diabetic by 310 days of age. In contrast to wild-type, 110-day-old ICAM-1 deficient females do not develop severe insulitis 10 days post cyclophosphamide treatment. Protection is associated with suppression of destructive insulitis as well as a deviation to a T-helper 2 cytokine mRNA expression pattern (Martin et al. 2001).
Both the C57BL/6 contaminated strain and the non contaminated strain, Stock No. 006351 - NOD.129S4(B6)-Icam1tm1Jcgr/J are completely diabetes resistant at 30 weeks of age when evaluated in a comparative diabetes incidence study. Fine mapping data may be viewed at GQC of Icam1 congenic stocks
NOD.129S4(B6)-Icam1tm1Jcgr/SmtnJ is useful for studying the ICAM-1/LAF-1 interaction and its role in diabetes.
Intercellular adhesion molecule 1 (Icam1), located on Chr9, 7cM, contains 7 exons and is one of the immunoglobulin superfamily that binds to the integrins LFA-1 and Mac-1 on leukocytes. A neomycin resistance cassette was inserted into exon 4 (one of the 5 Ig-like extracellular domains) of the Icam1 gene. J1 ES cell clone 74 was injected into B6 blastocysts. This Icam1 mutation has been backcrossed to NOD for at least 6 generations (Martin et al, 2001). The Type 1 Diabetes Resource received NOD.129S4(B6)-Icam1tm1Jcgr/SmtnJ in 2005.
Additional genetic quality control performed at The Jackson Laboratory indicates C57BL/6 genomic contamination on Chromosomes 6 and 7. Markers D6Mit178, D6Mit52 and D6Mit135 on Chromosome 6 were segregating for both NOD and C57BL/6. Through selective breeding we have been able to make the Chromosome 6 markers of NOD origin only. Markers D7Mit139, D7Mit96 and D7Mit328 on Chromosome 7 were found to be of C57BL/6 origin. This stock is available with the Chromosome 7 genomic contamination and may affect the diabetes incidence.
|Allele Name||targeted mutation 1, Jose Carlos Gutierrez Ramos|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||ICAMtm1-jcgr; ICAM-1-; ICAM-1-deficient|
|Gene Symbol and Name||Icam1, intercellular adhesion molecule 1|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin resistance cassette was inserted into exon 4 of the gene. While King, et. al. (J:25530) reported the potential for the production of functional proteins arising from alternative transcripts, corresponding signals were undetected by immunohistochemical analysis of homozygous mutant mice.|
|Mutations Made By|| |
Dr. Jose-Carlos Gutierrez-Ramos, Millenium Pharmaceuticals