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Chromosome substitution strains: gene discovery, functional analysis, and systems studies

Abstract

Laboratory mice are valuable in biomedical research in part because of the extraordinary diversity of genetic resources that are available for studies of complex genetic traits and as models for human biology and disease. Chromosome substitution strains (CSSs) are important in this resource portfolio because of their demonstrated use for gene discovery, genetic and epigenetic studies, functional characterizations, and systems analysis. CSSs are made by replacing a single chromosome in a host strain with the corresponding chromosome from a donor strain. A complete CSS panel involves a total of 22 engineered inbred strains, one for each of the 19 autosomes, one each for the X and Y chromosomes, and one for mitochondria. A genome survey simply involves comparing each phenotype for each of the CSSs with the phenotypes of the host strain. The CSS panels that are available for laboratory mice have been used to dissect a remarkable variety of phenotypes and to characterize an impressive array of disease models. These surveys have revealed considerable phenotypic diversity even among closely related progenitor strains, evidence for strong epistasis and for heritable epigenetic changes. Perhaps most importantly, and presumably because of their unique genetic constitution, CSSs, and congenic strains derived from them, the genetic variants underlying quantitative trait loci (QTLs) are readily identified and functionally characterized. Together these studies show that CSSs are important resource for laboratory mice.

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Acknowledgments

NIH NCRR grant RR12305, a Grant-in-Aid for Scientific Research on Priority Areas of Comparative Genomics from MEXT of Japan, and The Bio-diversity Research Project of TRIC, ROIS supported this study, and Praemium Academiae of the Czech Academy of Sciences supported preparation of this review.

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Correspondence to Joseph H. Nadeau, Jiri Forejt or Toshihiko Shiroishi.

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Nadeau, J.H., Forejt, J., Takada, T. et al. Chromosome substitution strains: gene discovery, functional analysis, and systems studies. Mamm Genome 23, 693–705 (2012). https://doi.org/10.1007/s00335-012-9426-y

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  • DOI: https://doi.org/10.1007/s00335-012-9426-y

Keywords

  • Quantitative Trait Locus
  • Inbred Strain
  • Host Strain
  • Congenic Strain
  • Chromosome Substitution Strain