FEB 05, 2014 2:00 PM PST

The impact of genetic background in mouse and rat models: concerns and solutions

C.E. Credits: CE
Speaker
  • Associate Professor, Department of Molecular Carcinogenesis, The University of Texas - M.D. Anderson Cancer Center, USA
    Biography
      Dr. Fernando Benavides is Associate Professor and Director of the Genetic Services at MD Anderson Cancer Center, Smithville, Texas, USA. He is a laboratory animal veterinarian and geneticist with extensive experience in describing mouse models involving spontaneous mutations. Dr. Benavides received a D.V.M (1986) and a Ph.D. (1998) from the University of Buenos Aires, Argentina. His Ph.D. training program was done at the laboratory of Dr. Jean-Louis Gunet at Institut Pasteur, Paris, France. Dr. Benavides is a diplomate of the American College of Laboratory Animal Medicine (ACLAM) since 2003 and he serves as Chief IACUC veterinarian for the MD Anderson Smithville campus. The overall goal of his research is to define new mouse models through forward genetics and as of June 2013 he has published 50 peer-reviewed publications plus books and book chapters on mouse genetics. As the Director of the Genetics Services he advises and coordinates speed congenics projects, genetic monitoring, background characterizations, and whole genome scans for MD Anderson investigators. He also provides free consultation on rodent genetics (including strain selection and standard nomenclature). He is regularly invited to give short courses and seminars on rodent genetics in many countries, including Argentina, Brazil, Chile, Mexico, Spain, and Uruguay.

    Abstract

    It is increasingly recognized that the genetic background (i.e., all genomic sequences other than the gene(s) of interest) can have profound influences on the phenotype of an animal model. It has been shown that mutations (spontaneous and induced), transgenes, and targeted alleles (knockouts and knockins) that are moved onto a different background can show a change in phenotype. One of the first cases involved the classical diabetes (Leprdb) mutation that presented transient diabetes on a C57BL/6 background but overt diabetes on C57BLKS. Other examples include background effects on survival rate in Egfr (epidermal growth factor receptor) KO mice and effects on tumor incidence and spectrum in Trp53 and Pten (tumor suppressors) KO mice. In order to highlight the importance of this issue, I will present a selection of published articles showing the influence of genetic background on different mouse and rat models. I will also discuss some of the problems arising from the use of undefined substrains, the use of genetically engineered mice with mixed backgrounds (e.g., after breeding chimeras), as well as the flanking genes and passenger mutations concerns. Finally, I will present different ways to avoid or resolve these drawbacks, including the development of congenic strains by marker-assisted backcrossing and the use of newly available ES cells from strains other than 129. In order to stay away from confounding or unreliable experimental results, particularly with the increasing number of mouse and rat strains, attention to the genetic background is crucial.


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