1. Association of extensive polymorphisms in the SLAM/CD2 gene cluster with murine lupus.
- Author
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Wandstrat AE, Nguyen C, Limaye N, Chan AY, Subramanian S, Tian XH, Yim YS, Pertsemlidis A, Garner HR Jr, Morel L, and Wakeland EK
- Subjects
- Alleles, Amino Acid Sequence, Animals, Animals, Congenic, Antigens, CD, Autoimmunity genetics, Autoimmunity immunology, CD2 Antigens chemistry, CD2 Antigens immunology, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes pathology, Calcium metabolism, Cell Differentiation, Glycoproteins chemistry, Glycoproteins immunology, Haplotypes genetics, Humans, Immunoglobulins chemistry, Immunoglobulins immunology, Lupus Erythematosus, Systemic immunology, Lupus Erythematosus, Systemic metabolism, Lupus Erythematosus, Systemic pathology, Lymphocyte Activation genetics, Lymphocyte Activation immunology, Mice, Molecular Sequence Data, Receptors, Cell Surface, Sequence Analysis, DNA, Signaling Lymphocytic Activation Molecule Family, Signaling Lymphocytic Activation Molecule Family Member 1, CD2 Antigens genetics, Glycoproteins genetics, Immunoglobulins genetics, Lupus Erythematosus, Systemic genetics, Multigene Family genetics, Polymorphism, Genetic genetics
- Abstract
Susceptibility to autoimmunity in B6.Sle1b mice is associated with extensive polymorphisms between two divergent haplotypes of the SLAM/CD2 family of genes. The B6.Sle1b-derived SLAM/CD2 family haplotype is found in many other laboratory mouse strains but only causes autoimmunity in the context of the C57Bl/6 (B6) genome. Phenotypic analyses have revealed variations in the structure and expression of several members of the SLAM/CD2 family in T and B lymphocytes from B6.Sle1b mice. T lymphocytes from B6.Sle1b mice have modified signaling responses to stimulation at 4-6 weeks of age. While autoimmunity may be mediated by a combination of genes in the SLAM/CD2 family cluster, the strongest candidate is Ly108, a specific isoform of which is constitutively upregulated in B6.Sle1b lymphocytes.
- Published
- 2004
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