International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 116 - GENETIC INFIDELITY AND INBRED MOUSE STRAINS

Wiles MV, Chu T, Palmer JH

The Jackson Laboratory, Bar Harbor, United States

Abstract: The use of mice and, in particular, genetically engineered mice to study normal and pathological biology pathways has increased exponentially in the last decade. One impetus for this has been the completion of sequence drafts for human, mouse and recently the rat genomes. The complexity, depth and associated high cost of information which can now be acquired from exploring mouse model systems mean that strict, stable genetic standards are paramount.

The genomes of all living organisms, including inbred mice, are however, continually evolving. Any genetic change in a strain can potentially lead to phenotypic change. For example, it was reported that a C57BL/6 substrain from Olac-Harlan-Sprague Dawley, UK was supplied for a few years with an undetected spontaneous deletion of more than 97kb, covering in part the alpha-synuclein locus, a gene implicated in a number of neurodegenerative diseases. These naturally occurring, accumulated genetic variations (genetic drift) can lead to unexpected results and confound deep data acquisition, making reliable comparative analysis on large data sets derived over time difficult. Furthermore, genetic contamination of inbred strains can occur even in the best mouse house leading to unexpected and confounding outcomes. It is therefore critical for any research organization to ensure that mice used are of the correct genotype and have not become a non standard subline.

We present how The Jackson Laboratory controls for genetic contamination and is reducing genetic drift to almost negligible levels by continual Genetic Quality Control monitoring and the creative use of in vitro fertilization and cryopreservation. The upholding of stable genetic standards for inbred lines enables the international community to develop valid massive comparative data sets which can be used for the foreseeable future. Support Contributed By: HMMI, The Ellison Medical Foundation and The Jackson Laboratory

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