Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  1
• Reference
  J:223540 Noordmans GA, et al., Genetic analysis of intracapillary glomerular lipoprotein deposits in aging mice. PLoS One. 2014;9(10):e111308
• ID
  MGI:5881806

Genes

Gene
Renaq1
Esrrg

Notes

• Experiment
  Several renal glomerular diseases show abnormal lipid deposits, the human disorder lipoprotein glomerulopathy (LPG) also shows intracapillary glomerular deposits. The current study was a part of the comprehensive aging study carried out by The Nathan Shock Center at the Jackson Laboratory. Age related phenotypes were measured every six months and made available on the Mouse Phenome Database (www.jax.org/phenome).
  
  Both kidneys from twenty six inbred strains of mice, ten males from each strain, were sacrificed at 6, 12 and 20 months of age for histopathological and molecular evaluation. For morphological evaluation periodic acid-Schiff (PAS) staining was performed; each animal was evaluated for the presence of glomerular intracapillary deposits. A glomerular phenotype, characterized by PAS-positive intracapillary deposits in the glomeruli, was noted in 6 of the 26 strains: NOD.B10Sn-H2^b/J (NOD), NZW/LacJ (NZW), NON/ShiLtJ (NON), C57BL/10J (B10), C3H/HeJ (C3H) and C57BR/cdJ (C57BR). The strains that contained deposits at an age of 20 months were also evaluated at 12 months to study the association of the deposits with aging. From the 12 month old mice only NON and NOD showed PAS positive deposits. At 6 months of age NON mice showed a glomerular deposit score that depicted the age associated increase in glomerular deposits.
  
  Association mapping for glomerular intracapillary deposits was performed using the Efficient Mixed Models Association. The strain mean was used as the phenotype input and analysis was carried out using 274,648 informative SNPs from the Mouse Diversity Genotyping Array. For each SNP the association between genotype and phenotype was analyzed individually and a p-value was recorded as the strength of the genotype-phenotype association. Associations with a p-value of less than 10(-6) were the focus; a p-value of less than 0.05 was considered statistically significant.
  
  The genome wide haplotype association mapping (HAM) results for glomerular intracapillary deposits in males at 20 months of age identified a small 30 kb haplotype block on Chromosome 1 of six SNPs, between rs48848476 and rs46020199, within the Esrrg gene with a p-value of 0.0000000959 which was different between strains with glomerular deposits and those without glomerular deposits. MGI Curators have named the region, identified in the NON strain, as QTL Renaq1 (renal againg QTL 1).
  
  In a 1 Mb region either side if the haplotype block genes Spata17, Gpatch2, Esrrg, Ush2a and Kctd3 were identified (NCBI m37 assembly). Comparing genome sequences using the Sanger Institute Mouse Genome database no sequence differences in the coding regions of the five genes, between the strains with and without glomerular deposits, were found. Realtime PCR for the same five genes on kidney RNA, from several strains with and without glomerular deposits, showed a high expression of all genes in the kidney but no significant difference in expression levels between strains with and without deposits.