Lngrn1^KK/HlJ
QTL Variant Detail

Summary

• QTL variant: Lngrn1^KK/HlJ
• Name: lung airway resistance QTL 1; KK/HlJ
• MGI ID: MGI:6379605
• QTL: Lngrn1 Location: unknown Genetic Position: Chr2, Syntenic

Variant origin

• Strain of Specimen: KK/HlJ

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

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

J:276610

Vitamin D receptor (VDR) polymorphisms are associated with an increased asthma incidence in human populations; however, observations in Vdr knockout mice are unclear. The aim of this study was to determine the influence of the genetic variation in Vdr among inbred strains on lung resistance (i.e., dynamic and airway resistance).

KK/HlJ and C57BL/6J mice were mated to produce (KK/HlJ x C57BL/6J)F1 and (C57BL/6J x KK/HlJ)F1 reciprocal progeny. The (KK/HlJ 9 C57BL/6J)F1 progeny were intercrossed to produce an F2 population of 147 females and 132 males.

Lung functions were measured in 11-week-old mice by invasive forced oscillation technique. A total of 379 SNP markers were polymorphic between KK/HlJ and C57BL/6J. All QTL analyses were performed with the R/qtl software package (v. 1.18-7). All genome coordinates relative to NCBI B37 (mm9).

The authors detected three single main-effect loci for phenotypic differences among the F2 progeny:

Lngrn1 (lung airway resistance QTL 1) maps to Chr 2: 73.9 - 103.8 Mb with a peak LOD score of 3.8 at 79.9 cM. The C57BL/6J allele increases lung airway resistance at Lngrn1 in an intermediate manner.

Lngrn2 (lung airway resistance QTL 2) maps to Chr 3: 12.0 - 40.0 Mb with a peak LOD score of 3.8 at 20.3 cM. The KK/HlJ allele increases lung airway resistance at Lngrn2 in a recessive manner.

Lngr1 (lung dynamic resistance QTL 1) maps to Chr X: 28.5 - 56.5 Mb with a peak LOD score of 4.8 at 32.5 cM. The C57BL/6J allele increases lung dynamic resistance at Lngr1.

The authors found that the significant main-effect QTL on Chr X for increase in dynamic resistance interacts with QTL on Chr 7 at 74.5 cM, Chr 15 at 53.8 cM, and Chr 17 at 17 cM. The gene encoding vitamin D receptor (Vdr) maps to the peak of the interacting Chr 15 QTL.

Several suggestive QTL were also identified and are described in Table 2 of the publication text.

The authors examined the genotypes of Vdr among the 36 strains from their previous survey for airway responsiveness (Leme et al. 2010) using the SNP wizard from the Mouse Phenome Database. They grouped the strains according to their genotype differences [known to cause a change in the amino acid (non-synonymous SNPs,

Cn SNPs)] into a KK/HlJ-like and C57BL/6J-like group. Groups were compared for airway resistance.

Strains with a C57BL/6J-like genotype on the Vdr locus had significantly lower airway resistance than strains with a KK/HlJ-like genotype. Vdr knockout mice were examined for dynamic resistance and showed significantly higher resistance than mice with one (i.e., heterozygous) or both copies (i.e., wild-type) of the Vdr. In comparison to C57BL/6J, the strain A/J is more resistant but carries the same genotype at the Vdr locus. Dietary vitamin D manipulation in the strain A/J did not rescue the high airway resistance phenotype.

References

• Original: J:276610 Berndt A, et al., Genetic analysis of lung function in inbred mice suggests vitamin D receptor as a candidate gene. Mol Genet Genomics. 2011 Oct;286(3-4):237-46
• All: 1 reference(s)