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Int. J. Mol. Sci. 2015, 16(7), 15031-15056; doi:10.3390/ijms160715031

Differences between Mice and Humans in Regulation and the Molecular Network of Collagen, Type III, Alpha-1 at the Gene Expression Level: Obstacles that Translational Research Must Overcome

1
Department of Orthopedic Surgery and BME-Campbell Clinic, University of Tennessee Health Science Center, Memphis, TN 38163, USA
2
Department of Basic Research, Inner Mongolia Medical College, Inner Mongolia 010110, China
3
Integrative Research Center, the first Hospital of Qiqihaer City, Qiqihaer 161005, China
4
Department of Medicine, Mudanjiang Medical College, Mudanjiang 157001, China
5
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030, USA
6
Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
7
Research Service, Veterans Affairs Medical Center, Memphis, TN 38104, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 24 March 2015 / Revised: 8 June 2015 / Accepted: 9 June 2015 / Published: 3 July 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Collagen, type III, alpha-1 (COL3A1) is essential for normal collagen I fibrillogenesis in many organs. There are differences in phenotypes of mutations in the COL3A1 gene in humans and mutations in mice. In order to investigate whether the regulation and gene network of COL3A1 is the same in healthy populations of mice and humans, we compared the quantitative trait loci (QTL) that regulate the expression level of COL3A1 and the gene network of COL3A1 pathways between humans and mice using whole genome expression profiles. Our results showed that, for the regulation of expression of Col3a1 in mice, an eQTL on chromosome (Chr) 12 regulates the expression of Col3a1. However, expression of genes in the syntenic region on human Chr 7 has no association with the expression level of COL3A1. For the gene network comparison, we identified 44 top genes whose expression levels are strongly associated with that of Col3a1 in mice. We next identified 41 genes strongly associated with the expression level of COL3A1 in humans. There are a few but significant differences in the COL3A1 gene network between humans and mice. Several genes showed opposite association with expression of COL3A1. These genes are known to play important roles in development and function of the extracellular matrix of the lung. Difference in the molecular pathway of key genes in the COL3A1 gene network in humans and mice suggest caution should be used in extrapolating results from models of human lung diseases in mice to clinical lung diseases in humans. These differences may influence the efficacy of drugs in humans whose development employed mouse models. View Full-Text
Keywords: COL3A1; gene network; human; mouse; lung fibrosis COL3A1; gene network; human; mouse; lung fibrosis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wang, L.; Liu, H.; Jiao, Y.; Wang, E.; Clark, S.H.; Postlethwaite, A.E.; Gu, W.; Chen, H. Differences between Mice and Humans in Regulation and the Molecular Network of Collagen, Type III, Alpha-1 at the Gene Expression Level: Obstacles that Translational Research Must Overcome. Int. J. Mol. Sci. 2015, 16, 15031-15056.

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