Mapping Data

Experiment

• Experiment
  TEXT
• Chromosome
  4
• Reference
  J:107391 Cook DN, et al., Spontaneous mutations in recombinant inbred mice: mutant toll-like receptor 4 (Tlr4) in BXD29 mice. Genetics. 2006 Mar;172(3):1751-5
• ID
  MGI:3626081

Genes

Gene	Assay Type
Tlr4	reported elsewhere

Notes

• Experiment
  BXD29/TyJ is a recombinant inbred strain that is unresponsive to aerosolized lipopolysaccharide (LPS). BXD29/TyJ is derived from parental strain DBA/2J (highly responsive) and C57BL/6J (somewhat responsive). The phenotype segregates as a single recessively-inherited locus. To map the gene responsible for LPS-unresponsiveness in BXD29/TyJ mice, 300 polymorphic loci were genotyped in a pool of 25 responsive and 25 non-responsive (BXD29/TyJ x DBA/2J)F2 animals. A locus at 40 cM on mouse Chromosome 4 is highly associated with homozygosity for C57BL/6J-derived alleles in non-responsive F2 animals.
  
  Tlr4 maps close to this locus at 34 cM. Tlr4 is required for LPS response and was investigated as a candidate gene. Complementation analysis was performed by assessing (BXD29TyJ x C57BL/6J-Tlr4)F1 animals for inhaled LPS responsiveness. F1 animals were non-responsive and indistinguishable from C57BL/6J-Tlr4 animals, suggesting that the mutation in BXD29/TyJ which results in LPS nonresponsiveness is allelic to Tlr4.
  
  PCR analysis revealed a large repetitive element inserted into exon 3 of the BXD29/TyJ Tlr4 sequence. Flow cytometric analysis showed that macrophages from BXD29/TyJ animals do not express Tlr4 on the cell surface.