A novel CD93 polymorphism in non-obese diabetic (NOD) and NZB/W F1 mice is linked to a CD4+ iNKT cell deficient state
Copyright policy )A novel CD93 polymorphism in non-obese diabetic (NOD) and NZB/W F1 mice is linked to a CD4+ iNKT cell deficient state
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.
- University of Pennsylvania United States
- Children's Hospital of Philadelphia United States
- University of California, Irvine United States
- University of California, San Francisco United States
CD4-Positive T-Lymphocytes, Immunology, Molecular Sequence Data, Mice, Nkt2, Mice, Inbred NOD, Genetics, Animals, Lymphocyte Count, iNKT cells, Original Paper, Mice, Inbred BALB C, Membrane Glycoproteins, Polymorphism, Genetic, Idd13, Base Sequence, Mice, Inbred NZB, Chromosome Mapping, Human Genetics, Cell Biology, Receptors, Complement, Mice, Inbred C57BL, Biomedicine, Allergology, CD93, NZB/W F1 mice, Natural Killer T-Cells, Gene Function, NOD mice
CD4-Positive T-Lymphocytes, Immunology, Molecular Sequence Data, Mice, Nkt2, Mice, Inbred NOD, Genetics, Animals, Lymphocyte Count, iNKT cells, Original Paper, Mice, Inbred BALB C, Membrane Glycoproteins, Polymorphism, Genetic, Idd13, Base Sequence, Mice, Inbred NZB, Chromosome Mapping, Human Genetics, Cell Biology, Receptors, Complement, Mice, Inbred C57BL, Biomedicine, Allergology, CD93, NZB/W F1 mice, Natural Killer T-Cells, Gene Function, NOD mice
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