Publication Details

Genome-wide analysis of hepatic fibrosis in inbred mice identifies the susceptibility locus Hfib1 on chromosome 15.

Authors:Hillebrandt S, Goos C, Matern S, Lammert F
Title:Genome-wide analysis of hepatic fibrosis in inbred mice identifies the susceptibility locus Hfib1 on chromosome 15.
Journal:Gastroenterology Dec 2002 , Vol 123 , pp. 2041-51
Abstract:Host genetic factors are likely to contribute to the variable course of hepatic fibrosis in response to chronic liver injury. Similarly, the fibrotic response differs among inbred mouse strains after challenge with CCl(4). Our aim was to identify unknown susceptibility loci for hepatic fibrosis in a cross between fibrosis-susceptible and -resistant inbred mice.Seven inbred mouse strains were treated with CCl(4), and hepatic fibrosis was phenotypically characterized by histology, hepatic hydroxyproline levels, and serum surrogate markers. F(1) hybrids of susceptible BALB/cJ and resistant A/J inbred strains were intercrossed to obtain 358 F(2) progeny. Quantitative trait loci (QTL) that determine hepatic fibrosis were identified by genome-wide interval mapping and haplotype analysis.In this model, marked strain differences in fibrosis susceptibility exist, with BALB/c inbred mice being most susceptible. The hydroxyproline levels of F(1) mice resemble the resistant parental strains, indicating that fibrosis susceptibility is a recessive trait. QTL analysis identifies a susceptibility locus on chromosome 15 that significantly affects the stage of fibrosis and hydroxyproline levels. According to standard nomenclature, this locus is called Hfib1 (hepatic fibrogenic gene 1). Hfib1 is defined by genetic markers D15Mit26 and D15Mit122. A suggestive QTL on chromosome 2 colocalizes with the complement factor 5 gene, known to be mutated in the resistant strain A.The set of inbred strains provides a framework for systematic analysis of fibrogenic genes. QTL mapping is useful to identify genetic susceptibility loci for hepatic fibrosis that might harbor new molecular targets for antifibrotic drug design.   PUBMED: 12454860
Ontological Annotations:
  • D006909: Hydroxyproline (Publication, NCBO Annotator)
  • D015415: Biological Markers (Publication, NCBO Annotator)
  • D040641: Quantitative Trait Loci (Publication, NCBO Annotator)
  • D044967: Serum (Publication, NCBO Annotator)
  • MA:0000358: liver (Publication, NCBO Annotator)
  • D002875: Chromosomes (Publication, NCBO Annotator)
  • D005819: Genetic Markers (Publication, NCBO Annotator)
  • D006653: Histology (Publication, NCBO Annotator)
  • D006239: Haplotypes (Publication, NCBO Annotator)
  • D003165: Complement System Proteins (Publication, NCBO Annotator)
  • D051379: Mice (Publication, NCBO Annotator)
  • D005355: Fibrosis (Publication, NCBO Annotator)
  • GO:0018995: host (Publication, NCBO Annotator)
  • GO:0005694: chromosome (Publication, NCBO Annotator)
  • D015195: Drug Design (Publication, NCBO Annotator)
  • D000339: Affect (Publication, NCBO Annotator)
  • D014947: Wounds and Injuries (Publication, NCBO Annotator)
  • D008815: Mice, Inbred Strains (Publication, NCBO Annotator)
  • D002884: Chromosomes, Human, Pair 15 (Publication, NCBO Annotator)
  • D020022: Genetic Predisposition to Disease (Publication, NCBO Annotator)
  • D020502: Terminology (Publication, NCBO Annotator)
  • MA:0002502: serum (Publication, NCBO Annotator)
  • MP:0003333: liver fibrosis (Publication, NCBO Annotator)
  • MP:0003045: fibrosis (Publication, NCBO Annotator)
  • D008099: Liver (Publication, NCBO Annotator)
  • D012718: Set (Psychology) (Publication, NCBO Annotator)
  • D002889: Chromosomes, Human, Pair 2 (Publication, NCBO Annotator)
  • D002678: Chimera (Publication, NCBO Annotator)

1 GeneSets from this Publication:

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Expand Tier II Mouse 485 Genes GS135992: hepatic fibrogenesis 1 (Hfib1, Published QTL Chr 15)