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ToxSci Advance Access originally published online on June 2, 2005
Toxicological Sciences 2005 87(1):277-284; doi:10.1093/toxsci/kfi214
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

HIGHLIGHTED ARTICLE

Metabonomic Identification of Two Distinct Phenotypes in Sprague-Dawley (Crl:CD(SD)) Rats

Lora C. Robosky*,1, Dale F. Wells*, Laura A. Egnash*, Matthew L. Manning{dagger}, Michael D. Reily* and Donald G. Robertson*

* Pfizer Global Research and Development, Metabonomics Evaluation Group, Ann Arbor, Michigan 48105, and {dagger} Manpower, Inc., 231 Little Lake Drive, Ann Arbor, Michigan 48103

Received April 20, 2005; accepted May 31, 2005

Genetic drift in animal populations has been a recognized concern for many years. Less understood is the potential for phenotypic "drift" or variation that is not related to any genetic change. Recently, stock Sprague-Dawley (Crl:CD(SD)) rats obtained from the Charles River Raleigh facility demonstrated a distinct endogenous urinary metabonomic profile that differed from historical control SD urine spectral profiles obtained over the past several years in our laboratory. In follow-up studies, the origin of the variant phenotype was narrowed down to animals of both sexes that were housed in one specific room (Room 9) in the Raleigh facility. It is likely that the two phenotypes are related to distinct populations of gut flora that particularly impact the metabolism of aromatic molecules. The most pronounced difference between the two phenotypes is the relative amounts of hippuric acid versus other aromatic acid metabolites of chlorogenic acid. Though both molecular species are present in either phenotype, the marked variation in levels of these molecules between the two phenotypes has led to the designation of high hippuric acid (HIP) and high chlorogenic acid metabolites (CA) phenotypes. Specific urinary components that distinguish the phenotypes have been thoroughly characterized by NMR spectroscopy with additional, limited characterization by LC-MS (high performance liquid chromatography coupled with mass spectrometry). Co-habitation of rats from the two phenotypes rapidly facilitated a switch of the CA phenotype to the historical Sprague-Dawley phenotype (HIP). The impact of these variant phenotypes on drug metabolism and long-term safety assessment studies (e.g., carcinogenicity bioassays) is unknown.

Key Words: metabonomics; phenotype; Sprague-Dawley (Crl:CD(SD)); hippuric acid; chlorogenic acid.


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