Heterogeneous stock rats: a new model to study the genetics of renal phenotypes. Am J Physiol Renal Physiol 2010 Jun;298(6):F1484-91
Date
03/12/2010Pubmed ID
20219828Pubmed Central ID
PMC2886820DOI
10.1152/ajprenal.00002.2010Scopus ID
2-s2.0-77952706580 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
Chronic kidney disease is a growing medical concern, with an estimated 25.6 million people in the United States exhibiting some degree of kidney injury and/or decline in kidney function. Animal models provide great insight into the study of the genetics of complex diseases. In particular, heterogeneous stock (HS) rats represent a unique genetic resource enabling rapid fine-mapping of complex traits. However, they have not been explored as a model to study renal phenotypes. To evaluate the usefulness of HS rats in the genetics of renal traits, a time course evaluation (weeks 8-40) was performed for several renal phenotypes. As expected, a large degree of variation was seen for most renal traits. By week 24, three (of 40) rats exhibited marked proteinuria that increased gradually until week 40 and ranged from 33.7 to 80.2 mg/24 h. Detailed histological analysis confirmed renal damage in these rats. In addition, several rats consistently exhibited significant hematuria (5/41). Interestingly, these rats were not the same rats that exhibited proteinuria, indicating that susceptibility to different types of kidney injury is likely segregating within the HS population. One HS rat exhibited unilateral renal agenesis (URA), which was accompanied by a significant degree of proteinuria and glomerular and tubulointerstitial injury. The parents of this HS rat were identified and bred further. Additional offspring of this pair were observed to exhibit URA at frequency between 40% and 60%. In summary, these novel data demonstrate that HS rats exhibit variation in proteinuria and other kidney-related traits, confirming that the model harbors susceptibility alleles for kidney injury and providing the basis for further genetic studies.
Author List
Solberg Woods LC, Stelloh C, Regner KR, Schwabe T, Eisenhauer J, Garrett MRAuthor
Kevin R. Regner MD Interim Chair, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlood Urea Nitrogen
Chronic Disease
Creatinine
Disease Models, Animal
Disease Progression
Genetic Predisposition to Disease
Genetic Variation
Glycosuria, Renal
Hematuria
Heterozygote
Kidney
Kidney Diseases
Phenotype
Proteinuria
Quantitative Trait, Heritable
Rats
Rats, Inbred BN
Rats, Inbred BUF
Rats, Inbred F344
Rats, Inbred WKY
Rats, Sprague-Dawley
Species Specificity
Time Factors
