Nktcn1^NOD/ShiLt
QTL Variant Detail

Summary

• QTL variant: Nktcn1^NOD/ShiLt
• Name: natural killer T cell numbers 1; NOD/ShiLt
• MGI ID: MGI:2681150
• Synonyms: Nktcn1^NOD
• QTL: Nktcn1 Location: Chr1:168186243-171632257 bp Genetic Position: Chr1, cM position of peak correlated region/allele: 76.25 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: NOD/ShiLt

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers decreased natural killer T cell numbers compared to C57BL/6J.
• Inheritance: Other (see notes)

Notes

Nktcn1 exhibits additive inheritance.

Candidate Genes

J:137521

Microarray analysis was performed on thymus RNA from 4 week old NOD.Nkrp1^b.Nkt1^b congenic animals and NOD.Nkrp1^b congenic animals to screen candidate genes for Nktcn1. The NOD.Nkrp1^b congenic carries C57BL/6J-derived DNA from D6Mit105 (45.5 cM) toD6Mit135 (62.3 cM) on a NOD genetic background. The NOD.Nkrp^b.Nkt1^b congenic carries C57BL/6J-derived DNA from D1Mit369 (73 cM) to D1Mit155 (telomere) on a NOD genetic background in addition to the NOD-derived chromosome 6 interval. The formal QTL designation for Nkt1 is Nktcn1. Nkrp1 is synonymous with Klrb1c. Previously identified lupus susceptibility locus Sle1b (89.5 cM) maps near Nktcn1.

Twenty-one genes displaying expression differences between NOD and C57BL/6J mapped to the Nktcn1 region, 15of which are located in the 95% confidence interval. The most promising candidate genes for controlling NKT cell number are Slamf1 (93.3 cM) and Slamf6 (89.5 cM). Gene expression of Slamf1 and Slamf6 was examined in thymic and splenic lymphocytes from congenic animals. It was observed that NOD.Nkrp^b.Nkt1^b animals expressed significantly higher amounts of SLAM proteins on cell sufaces compared to NOD.Nkt1^b parentals. Authors hypothesize control of NKT cell numbers may be mediated by differentialexpression of Slamf1 with additionial influence by Slamf6.

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

J:85376

Linkage analysis was performed on 138 (C57BL/6J x NOD.B6-(D6Mit105-D6Mit135))F1 x NOD.B6-(D6Mit105-D6Mit135) backcross animals to identify QTLs associated with natural killer T (NKT) cell numbers. 181 markers (90% genome coverage) at an average spacing of 8 cM were used in the genome scan. Parental strain C57BL/6J exhibits higher NKT cell numbers compared to parental strain NOD.Nkrp1^b. (C57BL/6J x NOD.B6-(D6Mit105-D6Mit135))F1 hybrid animals exhibit NKT cell numbers similar to the C57BL/6J parentals.

Nktcn1 (natural killer T cell numbers 1) was identified at 87.9 cM on mouse Chromosome 1 with LOD=6.82 at D1Mit15. Nktcn1 spans a 7 cM interval with C57BL/6J-derived alleles conferring increased NKT cell numbers with an additive mode of inheritance. Potential candidate genes mapping near Nktcn1 include Sele, Xcl1, Cd247, Fcgr2b, Fcgr3, and Cd244.

Nktcn2 was identified at approximately 73 cM on mouse Chromosome 2 with LOD=4.9 between D2Mit490 and D2Mit280. Nktcn2 spans a 3 cM interval with C57BL/6J-derived alleles conferring increased NKT cell numbers with an additive mode of inheritance. Potential candidate genes mapping near Nktcn2 include a yet unnamed heat shock protein and B2m.

Suggestive linkages to NKT cell numbers were also observed between 15 cM (D2Mit294) and 31.7 cM (D2Mit458) on mouse Chromosome 2 with LOD=1.92, at 60 cM (D7Mit101) on mouse Chromosome 7 with LOD=1.9, and at 22.5 cM (D17Mit176) near the MHC region of mouse Chromosome 17 with LOD=2.0.

References

• Original: J:85376 Esteban LM, et al., Genetic control of NKT cell numbers maps to major diabetes and lupus Loci. J Immunol. 2003 Sep 15;171(6):2873-8
• All: 3 reference(s)