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Modifier locus on mouse chromosome 3 for renal vascular pathology in AT1A receptor-deficiency.

Publication ,  Journal Article
Le, TH; Fogo, AB; Salzler, HR; Vinogradova, T; Oliverio, MI; Marchuk, DA; Coffman, TM
Published in: Hypertension
February 2004

We previously showed that the phenotype of mice with targeted disruption of the gene encoding the AT1A receptor (Agtr1a), the major murine AT1 receptor isoform, is strongly influenced by recessive genetic modifiers derived from the C57BL/6 or 129 inbred strains. To further evaluate the genetic modifiers on the C57BL/6 background, we performed backcrosses between F1(C57BL/6x129) and C57BL/6 Agtr1a-/- mice and analyzed the progeny, focusing on the development of structural lesions in the renal vasculature. In affected animals, these lesions are characterized by medial thickening of small arteries and arterioles in the kidney that are reminiscent of vascular lesions in patients with nephrosclerosis. Among 180 consecutive progeny, 170 (94%) survived to completion of the study. On masked pathological examination at age 8 months, 86 had intermediate to severe vascular lesions whereas 84 had no detectable lesions. Based on a hypothetical model of a single recessive modifier locus arising from the C57BL/6 background, the observed proportion of affected animals among the backcross progeny was not statistically different from that predicted by chi2 analysis (51% versus 50%; P=0.88). We next performed genomic microsatellite analysis in a subset of 121 backcross progeny using a panel of markers spanning approximately 15 cM intervals across the mouse genome. By 2-point analysis, we found a region spanning 5 cM on chromosome 3, with significant linkage to the development of renal vascular lesions (LOD score: 3.3 to 3.8).

Duke Scholars

Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

February 2004

Volume

43

Issue

2

Start / End Page

445 / 451

Location

United States

Related Subject Headings

  • Survival Analysis
  • Receptor, Angiotensin, Type 1
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Kidney Diseases
  • Kidney
  • Genetic Linkage
  • Crosses, Genetic
  • Chromosomes, Mammalian
 

Citation

APA
Chicago
ICMJE
MLA
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Le, T. H., Fogo, A. B., Salzler, H. R., Vinogradova, T., Oliverio, M. I., Marchuk, D. A., & Coffman, T. M. (2004). Modifier locus on mouse chromosome 3 for renal vascular pathology in AT1A receptor-deficiency. Hypertension, 43(2), 445–451. https://doi.org/10.1161/01.HYP.0000112423.28987.00
Le, Thu H., Agnes B. Fogo, Harmony R. Salzler, Tania Vinogradova, Michael I. Oliverio, Douglas A. Marchuk, and Thomas M. Coffman. “Modifier locus on mouse chromosome 3 for renal vascular pathology in AT1A receptor-deficiency.Hypertension 43, no. 2 (February 2004): 445–51. https://doi.org/10.1161/01.HYP.0000112423.28987.00.
Le TH, Fogo AB, Salzler HR, Vinogradova T, Oliverio MI, Marchuk DA, et al. Modifier locus on mouse chromosome 3 for renal vascular pathology in AT1A receptor-deficiency. Hypertension. 2004 Feb;43(2):445–51.
Le, Thu H., et al. “Modifier locus on mouse chromosome 3 for renal vascular pathology in AT1A receptor-deficiency.Hypertension, vol. 43, no. 2, Feb. 2004, pp. 445–51. Pubmed, doi:10.1161/01.HYP.0000112423.28987.00.
Le TH, Fogo AB, Salzler HR, Vinogradova T, Oliverio MI, Marchuk DA, Coffman TM. Modifier locus on mouse chromosome 3 for renal vascular pathology in AT1A receptor-deficiency. Hypertension. 2004 Feb;43(2):445–451.

Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

February 2004

Volume

43

Issue

2

Start / End Page

445 / 451

Location

United States

Related Subject Headings

  • Survival Analysis
  • Receptor, Angiotensin, Type 1
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Kidney Diseases
  • Kidney
  • Genetic Linkage
  • Crosses, Genetic
  • Chromosomes, Mammalian