Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  2
• Reference
  J:87690 Li N, et al., Gain-of-function polymorphism in mouse and human Ltk: implications for the pathogenesis of systemic lupus erythematosus. Hum Mol Genet. 2004 Jan 15;13(2):171-9
• ID
  MGI:3042397

Genes

Gene	Assay Type
Aabpr	visible phenotype
D2Mit254	PCR amplified length variant
Ltk	reported elsewhere
Tyro3	reported elsewhere
B2m	reported elsewhere
Plcb2	reported elsewhere

Notes

• Experiment
  Genome scan at a resolution of 10 cM was performed on 261 (NZB/Slc x NZW/Slc)F1 x NZB/Slc backcross animals to identify QTLs associated with the aberrant proliferation of peripheral B1 cells, a phenotype associated with systemic lupus erythematosus. Parental strain NZB/Slc exhibits high frequencies of B1 cell activation in conjunction with IgM hypergammaglobulinemia compared to parental strain NZW/Slc.
  
  Abpr (aberrant B cell proliferation) mapped to 65.5 cM on mouse Chromosome 2 (LOD=3.56) spanning the flanking markers D2Mit254 and D2Mit30 [Fig 2]. NZB/Slc-derived alleles confer increased activation of self-reactive B1 cells at this locus.
  
  Several candidate genes map near Abpr and include Ltk (67 cM), Plcb2 (67 cM), Tyro3 (67.1 cM), and B2m (69 cM). Sequence analysis of Ltk revealed a single nucleotide polymorphism (SNP) between NZB/Slc and NZW/Slc strains at nucleotide 1517 (NZB/Slc=A, NZW/Slc=G). This SNP translates to a glutamic acid to glycine amino acid substitution at residue 746 in the kinase domain. When the SNP is typed for linkage to B cell proliferation the LOD score increases to 4.80. The SNP also shows linkage to serum IgM levels (LOD=3.13). Studies with human SLE patients showed correlation of the 746K allele to disease. Ltk is considered a strong candidate gene by the authors.
  
  Functional assays involving the mouse and human Ltk 746K alleles suggested a role of this variant in upregulating the P13K pathway.