Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  15
• Reference
  J:208364 Poe JC, et al., EndoU is a novel regulator of AICD during peripheral B cell selection. J Exp Med. 2014 Jan 13;211(1):57-69
• ID
  MGI:6756390

Genes

Gene	Assay Type
Bdal1	visible phenotype

Notes

• Experiment
  Balanced transmembrane signals maintain a competent peripheral B cell pool limited in selfreactive B cells that may produce pathogenic autoantibodies. To identify molecules regulating peripheral B cell survival and tolerance to self-antigens (Ags), a gene modifier screen was performed with B cells from CD22-deficient C57BL/6 (B6.129-Cd22^tm2Tft/Tft; CD22^-/-[B6]) mice that undergo activation-induced cell death (AICD) and fail to up-regulate c-Myc expression after B cell Ag receptor ligation.
  
  Blast development after BCR ligation was assessed for purified spleen B cells from CD22^-/-[N1] littermates, along with B cells from single parental CD22^-/-[B6] and CD22^-/-[inbr] mice as controls. The results of 10 independent experiments were pooled. To reduce variability between mice and experiments, CD22^-/-[N1] mice B cell blast frequencies >1 SD above the mean percentage blasts were considered viable, whereas B cell blast frequencies <1 SD below the mean were considered nonviable.
  
  Genomic DNA from 22 viable and 22 nonviable CD22^-/-[N1] mice was used for genome-wide genotyping of 250 relevant SNPs between B6 and 129 mice (Illumina BeadArray; Duke University Genotyping Facility). QTL mapping used MapManager QTX regression analysis software (version QTXb20; Manly et al., 2001). Informative SNPs between B6 and 129 mice were identified using the Mouse Genome Informatics and dbSNP databases.
  
  Quantitative trait loci (QTL) mapping regression analysis revealed a single locus with high logarithm of odds (LOD) scores (P < 10^-6) on the distal end of chromosome (Chr) 15 with four consecutive SNPs spanning the region from 68 - 91 megabase pairs. LOD scores from the first three SNPs (68, 71, and 78 Mbp) were 8.3, increasing to 12.6 for the distal SNP (91 Mbp). The increased LOD score at 91 Mbp resulted from two mice (#14 and 28) with additional crossovers that were concordant with the observed phenotype. Parental CD22^-/-[B6] mice were homozygous B6:B6 within the identified locus (68 - 91 Mbp), whereas CD22^-/-[inbr] mice were homozygous 129:129. All other SNPs on Chr 15 outside of this locus (3.8 - 53 and 102 Mbp) were homozygous B6:B6 in all mice. Therefore, the primary genetic element responsible for CD22^-/-[B6] B cell AICD was located within a 24 Mbp region.
  
  Bdal1 (blast development after BCR ligation 1) maps to Chr 15: 68 - 91 Mb with a peak LOD score of 12.6 at 91 Mb (genome coordinates relative to GRCm38/mm10).
  
  EndoU was identified in a gene modifier screen as a unique and potent regulator of B cell AICD.