Original Article

X chromosome inactivation patterns in normal and X-linked hereditary nephropathy carrier dogs
R.J. Bell^a, G.E. Lees^b, K.E. Murphy^a

Departments of
^aPathobiology and
^bSmall Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX (USA)

Address of Corresponding Author

Cytogenet Genome Res 2008;122:37-40 (DOI: 10.1159/000151314)

  Abstract.

Alport syndrome (AS) and hereditary nephropathy (HN) are glomerular nephropathies caused by mutations in the genes encoding the type IV collagens. In a mixed breed of dog, termed Navasota (NAV) dogs, X-linked hereditary nephropathy (XLHN) is caused by a 10-bp deletion in exon 9 of COL4A5. Males harboring this mutation succumb to end-stage renal disease before 18 months of age. In contrast, female carriers of this disease survive much longer, most have a normal life-span, and vary in disease progression as compared with XLHN-affected males. X chromosome inactivation (XCI) patterns have been studied in human X-linked AS carriers and some have been shown to have a high degree of skewed XCI. However, similar studies have never been reported in an animal model of this disease. Therefore, patterns of XCI were examined in XLHN-carrier NAV dogs. The variation in XCI among the 26 XLHN-carrier and seven normal female NAV dogs studied was low and only three were found to preferentially inactivate one X chromosome, all of which were XLHN-carriers. The average skewedness among all dogs was 59% and 57% among the XLHN-carriers. No significant difference in XCI was found between the two groups (P = 0.477). It is clear from these data that genotype does not seem to have an effect on inactivation; the majority of these dogs have random patterns of XCI. Highly skewed X chromosome inactivation also appears to be random, given that no difference was observed between the XLHN-carriers and normal females. Because of the apparent rarity of skewed XCI, these dogs may not be a suitable model for studying a potential correlation between this phenomenon and disease progression.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Request reprints from Keith E. Murphy, Ph.D.
Department of Pathobiology
College of Veterinary Medicine and Biomedical Sciences
Texas A&M University, College Station, TX 77843-4467 (USA)
telephone: +1 979 845 2720; fax: +1 979 845 9231
e-mail: kmurphy@cvm.tamu.edu

  Article Information

Accepted in revised form for publication by J. Greally,: 3 June 2008.
Published online: October 14, 2008
Number of Print Pages : 4
Number of Figures : 2, Number of Tables : 0, Number of References : 16