title: Genetic analysis of intracapillary glomerular lipoprotein deposits in aging mice.
abstract: BACKGROUND
  Renal aging is characterized by functional and structural changes like decreased glomerular filtration rate, and glomerular, tubular and interstitial damage. To gain insight in pathways involved in renal aging, we studied aged mouse strains and used genetic analysis to identify genes associated with aging phenotypes.
  
  
  METHODS
  Upon morphological screening in kidneys from 20-month-old mice from 26 inbred strains we noted intracapillary PAS-positive deposits. The severity of these deposits was quantified by scoring of a total of 50 glomeruli per section (grade 0-4). Electron microscopy and immunohistochemical staining for apoE, apoB, apoA-IV and perilipin-2 was performed to further characterize the lesions. To identify loci associated with these PAS-positive intracapillary glomerular deposits, we performed haplotype association mapping.
  
  
  RESULTS
  Six out of 26 mouse strains showed glomerular PAS-positive deposits. The severity of these deposits varied: NOD(0.97), NZW(0.41), NON(0.30), B10(0.21), C3 H(0.9) and C57BR(0.7). The intracapillary deposits were strongly positive for apoE and weakly positive for apoB and apoA-IV. Haplotype association mapping showed a strong association with a 30-Kb haplotype block on Chr 1 within the Esrrg gene. We investigated 1 Mb on each site of this region, which includes the genes Spata17, Gpatch2, Esrrg, Ush2a and Kctd3.
  
  
  CONCLUSIONS
  By analyzing 26 aged mouse strains we found that some strains developed an intracapillary PAS and apoE-positive lesion and identified a small haplotype block on Chr 1 within the Esrrg gene to be associated with these lipoprotein deposits. The region spanning this haplotype block contains the genes Spata17, Gpatch2, Esrrg, Ush2a and Kctd3, which are all highly expressed in the kidney. Esrrg might be involved in the evolvement of these glomerular deposits by influencing lipid metabolism and possibly immune reponses.
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Gerda A
authors.initials: GA
authors.lastname: Noordmans
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, United States of America.
authors.forename: Holly
authors.initials: H
authors.lastname: Savage
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Marcory C R F
authors.initials: MC
authors.lastname: van Dijk
authors.affiliation: Department of Human Movement Sciences, NUTRIM, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Schaart
authors.affiliation: Department of Pathology, Amsterdam Medical Center, Amsterdam, The Netherlands.
authors.forename: Marius A
authors.initials: MA
authors.lastname: van den Bergh Weerman
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jan-Luuk
authors.initials: JL
authors.lastname: Hillebrands
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, United States of America.
authors.forename: Ron
authors.initials: R
authors.lastname: Korstanje
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D008040:Genetic Linkage; D056426:Genetic Loci; D006239:Haplotypes; D007678:Kidney Glomerulus / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001053:Apolipoproteins; D002352:Carrier Proteins; D000070778:Perilipin-1; D010750:Phosphoproteins