title: 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.
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.
authors.affiliation: Department of Orthopedic Surgery and BME-Campbell Clinic, University of Tennessee Health Science Center, Memphis, TN 38163, USA. lwang37@uthsc.edu.|Department of Basic Research, Inner Mongolia Medical College, Inner Mongolia 010110, China. lwang37@uthsc.edu.
authors.forename: Lishi
authors.initials: L
authors.lastname: Wang
authors.affiliation: Integrative Research Center, the first Hospital of Qiqihaer City, Qiqihaer 161005, China. hliu48@uthsc.edu.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery and BME-Campbell Clinic, University of Tennessee Health Science Center, Memphis, TN 38163, USA. yjiao2@uthsc.edu.|Department of Medicine, Mudanjiang Medical College, Mudanjiang 157001, China. yjiao2@uthsc.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Integrative Research Center, the first Hospital of Qiqihaer City, Qiqihaer 161005, China. ewang5@uthsc.edu.
authors.forename: Erjian
authors.initials: E
authors.lastname: Wang
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030, USA. sclark@nso2.uchc.edu.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Clark
authors.affiliation: Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA. apostlet@uthsc.edu.|Research Service, Veterans Affairs Medical Center, Memphis, TN 38104, USA. apostlet@uthsc.edu.
authors.forename: Arnold E
authors.initials: AE
authors.lastname: Postlethwaite
authors.affiliation: Department of Orthopedic Surgery and BME-Campbell Clinic, University of Tennessee Health Science Center, Memphis, TN 38163, USA. wgu@uthsc.edu.|Research Service, Veterans Affairs Medical Center, Memphis, TN 38104, USA. wgu@uthsc.edu.
authors.forename: Weikuan
authors.initials: W
authors.lastname: Gu
authors.affiliation: Integrative Research Center, the first Hospital of Qiqihaer City, Qiqihaer 161005, China. qsdyyych@126.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D002877:Chromosomes, Human / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism; D053263:Gene Regulatory Networks; D006801:Humans; D008171:Lung Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D040641:Quantitative Trait Loci; D013045:Species Specificity; D026801:Synteny; D057170:Translational Research, Biomedical
chemical_list: D024061:Collagen Type III
keywords: COL3A1; gene network; human; lung fibrosis; mouse