Tcdel2^NOD/ShiLtDoi
QTL Variant Detail

Summary

• QTL variant: Tcdel2^NOD/ShiLtDoi
• Name: T cell clonal deletion 2; NOD/ShiLtDoi
• MGI ID: MGI:3575705
• QTL: Tcdel2 Location: unknown Genetic Position: Chr3, Syntenic

Variant origin

• Strain of Specimen: NOD/ShiLtDoi

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased % double positive and decreased % double negative T cells compared to C57BL/6. (J:97046)
• Inheritance: Dominant

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:97046

Linkage analysis was performed on 306 (C57BL/6-H2^g7 x NOD/LtDOI)F2 embryos (transgenic for Tg(TcraBDC2.5)1Doi and Tg(TcrbBDC2.5)2Doi) to identify QTLs associated with T cell clonal deletion. 147 SNP markers spanning 19 autosomes and spaced approximately 16 Mb apart were used for the genome scan. Parental strain NOD/LtDOI exhibits resistance to T cell clonal deletion compared to parental strain C57BL/6-H2^g7.

Significant linkage to %DP (double positive) and %DN (double negative) T cells mapped to 135 Mb on mouse Chromosome 1 (LOD=4.2 for %DP; LOD=5.51 for %DN). This locus explains 15.2% of the variance and is named Tcdel1 (T cell clonal deletion 1). NOD/LtDOI-derived alleles at Tcdel1 confer increased %DP and decreased %DN T cells in non-peptide supplemented cell cultures derived from F2 embryos with a dominant mode of inheritance. Potential candidate genes mapping near Tcdel1 are Pdcd1, Bcl2 (59.8 cM), and Ptprv. Pdcd1 and Bcl2 exhibit differential expression in cell cultures derived from NOD/LtDOI and C57BL/6-H2^g7 mice. Previously identified QTLs Idd5a (38.5 cM) and Idd5b (41 cM) map near Tcdel1.

Significant linkage to %DP and %DN T cells from F2-derived cultures using peptide-supplemented media mapped to mouse Chromosome 3 (LOD=14.2). This locus explains 31.2% of the variance and is named Tcdel2 (T cell clonal deletion 2). NOD/LtDOI-derived alleles at Tcdel2 confer increased %DP and decreased %DN T cells in peptide supplemented cell cultures derived from F2 embryos with a dominant mode of inheritance. Potential candidate genes are Narg1, Ash1l, Sh2d2a (42.6 cM), and Cd1d1 (48 cM). Previously identified QTL Idd17 (39 cM) overlaps with the Tcdel2 interval. Idd3 (19.2 cM) and Idd10 (48.5 cM) map to either side of the Tcdel2 interval.

Linkage to %CD8-SP (single positive) T cells mapped to central mouse Chromosome 7 (LOD=9.69). This locus is named Cspt (CD8 single positive T cells). The QTL interval is very broad, spanning approximately 20 Mb to 110 Mb. C57BL/6-derived alleles at Cspt confer increased %CD8-SP T cells with a dominant mode of inheritance.

J:122481

Linkage analysis was performed on 91 F2 animals from a (B6.Cg-H2^g7 Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi x NOD.Cg-Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi)F2 intercross to identify genetic loci associated with thymocyte clonal deletion. Parental strain NOD.Cg-Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi displays increased clonal deletion of CD8alphaalpha thymocytes. One hundred twenty SNP markers at a resolution of 19 Mb were genotyped.

A major locus for % double-positive cells and % CD8 alpha alpha cells mapped to 25 cM (50 Mb) on mouse Chromosome 3 with LOD=6.67. This QTL is very tightly linked to Tcdel2 and may represent the same locus. Previously identified diabetes QTL Idd3 (19.2 cM) maps near Tcdel2. Complementation studies between NOD.Cg-Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi and a line from Taconic Farms named NOD.Idd3R540 suggests that Tcdel2 and Idd3 are independent of one another.

Suggestive linkage to thymocyte clonal deviation mapped to distal mouse Chromosome 1. This locus is tightly linked to a QTL identified in a previous study by the same authors named Tcdel1 (T cell clonal deletion 1), and may represent the same QTL.

References

• Original: J:97046 Zucchelli S, et al., Defective Central Tolerance Induction in NOD Mice: Genomics and Genetics. Immunity. 2005 Mar;22(3):385-396
• All: 2 reference(s)