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Physiol. Genomics (August 2, 2005). doi:10.1152/physiolgenomics.00076.2005
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Submitted on March 31, 2005
Accepted on July 25, 2005

Digital transcriptome analysis indicates adaptive mechanisms in the heart of a hibernating mammal

Katharine M Brauch1, Nirish D Dhruv2, Eric A Hanse1, and Matthew T Andrews1*

1 Biology, University of Minnesota Duluth, Duluth, Minnesota, USA
2 Computer Science, University of Minnesota Duluth, Duluth, Minnesota, USA

* To whom correspondence should be addressed. E-mail: mandrews{at}d.umn.edu.

Survival of near freezing body temperatures and reduced blood flow during hibernation is likely the result of changes in the expression of specific genes. In this paper we describe a comprehensive survey of mRNAs in the heart of the thirteen-lined ground squirrel (Spermophilus tridecemlineatus) before and during hibernation. The heart was chosen for this study because it is a contractile organ that must continue to work despite body temperatures of 5°C and the lack of food for periods of 5-6 months. We used a digital gene expression assay involving high-throughput sequencing of directional cDNA libraries from hearts of active and hibernating ground squirrels to determine the identity and frequency of 3,532 expressed sequence tags (ESTs). Statistical analysis of the active and hibernating heart expression profile indicated the differential regulation of 48 genes based on a p ≤ 0.03 threshold. Several of the differentially expressed genes identified in this screen encode proteins that likely account for uninterrupted cardiac function during hibernation including those involved in metabolism, contractility, Ca2+ handling and low temperature catalysis. A sampling of genes showing higher expression during hibernation include phosphofructokinase (PFK), pancreatic triacylglycerol lipase (PTL), pyruvate dehydrogenase kinase 4 (PDK4), aldolase A, sarco(endo)plasmic reticulum calcium-ATPase 2a (SERCA2a), titin, and four and a half LIM domains protein 2 (FHL2). Genes showing reduced levels of expression during hibernation include CDK2-associated protein 1 (CDK2AP1), troponin C, phospholamban (PLB), calcium-calmodulin dependent protein kinase II (CaMKII), calmodulin (CaM), and four subunits of cytochrome c oxidase.




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