• Open Access

Characterization of the Genetic Basis for Autosomal Recessive Hereditary Nephropathy in the English Springer Spaniel


  • Results in this paper were previously presented in part at the 5th International Conference on Advances in Canine and Feline Genomics and Inherited Diseases, American Genetic Association, Baltimore, MD, September 22–25, 2010.
  • With the exception of DNA isolation from whole blood, all molecular genetics procedures were carried out at Clemson University (Nowend, Starr-Moss, Murphy). Whole blood DNA isolation, clinical veterinary examinations and testing, pathological studies, and transmission electron microscopy were performed at the College of Veterinary Medicine and Biomedical Sciences, Texas A&M University (Lees, Berridge, Clubb, Nabity). Immunostaining work was done at the University of Minnesota Medical School (Kashtan).

Corresponding author: K.E. Murphy, Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29634-0318; e-mail: kmurph2@clemson.edu.



Autosomal recessive hereditary nephropathy (ARHN) was diagnosed in 2 English Springer Spaniels (ESS), a breed not previously reported to be affected by hereditary nephropathy (HN).


To identify and characterize the genetic cause of ARHN in ESS.


Sixty-three ESS (2 with ARHN, 2 obligate carriers, and 59 others), 2 mixed-breed dogs with X-linked HN, and 2 English Cocker Spaniels (ECS) with ARHN were included.


ARHN was diagnosed based on transmission electron microscopy and immunostaining of kidney. DNA from affected dogs was screened for the mutation known to cause ARHN in ECS. Quantities of COL4A3,COL4A4, and COL4A5 mRNA transcripts in renal cortex were determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for ARHN-affected dogs and 7 other dogs. The coding regions of COL4A3 and COL4A4 were sequenced for the 2 ARHN-affected ESS and an unaffected dog. Exon 30 of COL4A4 was sequenced for all 63 ESS.


qRT-PCR indicated a significant reduction in transcript levels of both COL4A3 and COL4A4 mRNA in the kidney of ARHN-affected ESS. Sequencing identified a single nucleotide substitution in COL4A4 at base 2806 resulting in a premature stop codon. Thirteen of 25 related dogs were identified as carriers.

Conclusions and Clinical Importance

A mutation highly likely to cause ARHN in ESS has been identified.