Lptl2^DBA/2J
QTL Variant Detail

Summary

• QTL variant: Lptl2^DBA/2J
• Name: LPS-induced pulmonary TNF-alpha locus 2; DBA/2J
• MGI ID: MGI:3046333
• QTL: Lptl2 Location: unknown Genetic Position: Chr2, Syntenic

Variant origin

• Strain of Specimen: DBA/2J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased LPS-induced pulmonary TNF-alpha concentrations compared to C57BL/6J. (J:90647)

Notes

Lptl1 and Lptl2 appear to interact. Animals homozygous for DBA/2J-derived alleles at both Lptl1 and Lptl2 display the highest levels of pulmonary TNF-alpha.

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

J:90647

Linkage analysis was used to identify QTLs associated with endotoxin-induced airway disease in a population of (C57BL/6J x DBA/2J)F2 animals and 32 BXD RI strains. Animals were exposed to aerosolized LPS and the level of PMN (polymorphonuclear leukocytes) and TNF-alpha in the lungs was measured. Parental strain C57BL/6J is a low-responder strain whereas DBA/2J is a high-responder strain.

DNA from 25 high response animals and 25 low response animals from the (C57BL/6J x DBA/2J)F2 population were pooled. Genome scan was performed on the pooled DNA and linkage to PMN level was detected around 50 cM on mouse Chromosome 11. Enrichment for C57BL/6J DNA in the low response pool and enrichment for DBA/2J DNA in the high response pool was observed at this locus,which is named Lppl1 (LPS-induced PMN locus 1). C57BL/6J-derived alleles confer increased PMN concentration at Lppl1 (30% more PMN compared to animals carrying a DBA/2J-derived allele). The Lppl1 locus spans 35 cM and contains approximately 300 genes. Microarray gene expression analysis identified 28 possible candidate genes within the Lppl1 interval (such as Eif4a1 and Igtp.)

Loci associated with TNF-alpha concentration, Lptl1 and Lptl2, mapped to 45 cM on mouse Chromosome 11 and to 60 cM on mouse Chromosome 2, respectively. The QTL interval of Lptl1 spans 25 cM - 60 cM and overlaps with Lppl1. DBA/2J-derived alleles confer increased pulmonary TNF-alpha levels at Lptl1 but the effect is greatest when the genotype is also homozygous for DBA/2J-derived alleles at Lptl2. The QTL interval of Lptl2 spans 50 cM - 75 cM. DBA/2J-derived alleles confer increased TNF-alpha levels at Lptl2 with dominant inheritance (59% more TNF-alpha compared to animals carrying C57BL/6J-derived alleles). The Lptl2 interval contains 160 genes. Microarray gene expression analysis identified approximately 10 possible candidate genes for Lptl2.

Lptl1 and Lptl2 appear to interact. Animals homozygous for DBA/2J-derived alleles at both Lptl1 and Lptl2 display the highest levels of pulmonary TNF-alpha.

References

• Original: J:90647 Cook DN, et al., Genetic regulation of endotoxin-induced airway disease. Genomics. 2004 Jun;83(6):961-9
• All: 1 reference(s)