NOD.129S4(B6)-Icam1^tm1Jcgr/J

Stock number: 006351
Product name: NOD.Icam1 KO clean
Research areas: Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research

Description

NOD mice homozygous for this targeted mutation of the intercellular adhesion molecule 1 (Icam1) gene are diabetes resistant. Diabetes resistance is associated with suppression of destructive insulitis and a deviation to a T-helper 2 cytokine mRNA expression pattern. This strain may be used to research the ICAM-1/LAF-1 interaction and its role in diabetes.

Detailed description

Homozygous mutant mice are diabetes resistant. No membrane bound ICAM-1 is detectable in homozygous mutant mice. Histological examination shows no or only mild peri-insular infiltration at 330-410 days of age, By comparison, 64% of their wild-type and 44% of their heterozygote cohorts 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, Stock No. 005983 - NOD.129S4(B6)-Icam1^tm1Jcgr/SmtnJ, and this non contaminated strain are completly 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

This targeted mutant strain is useful for studying the ICAM-1/LAF-1 interaction and its role in diabetes.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

Intercellular adhesion molecule 1 (Icam1), located on Chr 9, 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 Stock No. 005983 - NOD.129S4(B6)-Icam1^tm1Jcgr/SmtnJ in 2005. Shortly after arriving at The Jackson Laboratory additional genetic quality control indicated C57BL/6 genomic contamination on Chr 6 and 7. Markers D6Mit178, D6Mit52 and D6Mit135 on Chr 6 were segregating for both NOD and C57BL/6. Through selective breeding the Chr. 6 markers are NOD in origin. Markers D7Mit139, D7Mit96 and D7Mit328 on Chr 7 were found to be of C57BL/6 origin. After 2 crosses to NOD/ShiLtJ, all three Chr 7 markers were homozygous for the NOD-derived alleles. In 2007, this strain is at generation N?+N2F2.

Allele

Symbol: Icam1^tm1Jcgr
Name: targeted mutation 1, Jose Carlos Gutierrez Ramos
MGI accession ID: MGI:1857292
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Icam1
Marker name: intercellular adhesion molecule 1
Chromosome: 9
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.