1. A novel CD93 polymorphism in non-obese diabetic (NOD) and NZB/W F1 mice is linked to a CD4+ iNKT cell deficient state.
- Author
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Zekavat G, Mozaffari R, Arias VJ, Rostami SY, Badkerhanian A, Tenner AJ, Nichols KE, Naji A, and Noorchashm H
- Subjects
- Animals, Base Sequence, Chromosome Mapping, Lymphocyte Count, Membrane Glycoproteins physiology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, Inbred NZB, Molecular Sequence Data, Receptors, Complement physiology, CD4-Positive T-Lymphocytes immunology, Membrane Glycoproteins genetics, Natural Killer T-Cells immunology, Polymorphism, Genetic, Receptors, Complement genetics
- Abstract
In the present study, we characterize a polymorphism in the CD93 molecule, originally identified as the receptor for the C1q complement component (i.e., C1qRp, or AA4.1) in non-obese diabetic (NOD) mice. This allele carries a coding polymorphism in the first epidermal growth factor-like domain of CD93, which results in an amino acid substitution from Asn-->His at position 264. This polymorphism does not appear to influence protein translation or ecto-domain cleavage, as CD93 is detectable in bone-marrow-derived macrophage and B-cell precursor lysates and in soluble form in the serum. The NOD CD93 isoform causes a phenotypic aberrancy in the early B-cell developmental stages (i.e., pro-, pre-, immature, and transitional), likely related to a conformational variation. Interestingly, the NZB/W F1 strain, which serves as a murine model of Lupus, also expresses an identical CD93 sequence polymorphism. Cd93 is located within the NOD Idd13 locus and is also tightly linked to the NZB/W F1 Wbw1 and Nkt2 disease susceptibility loci, which are thought to regulate natural killer T (NKT) cell homeostasis. Consistent with this genetic linkage, we found B6 CD93(-/-) and B6.NOD(Idd13) mice to be susceptible to a profound CD4(+) NKT cell deficient state. These data suggest that Cd93 may be an autoimmune susceptibility gene residing within the Idd13 locus, which plays a role in regulating absolute numbers of CD4(+) NKT cells.
- Published
- 2010
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