International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


Ching Y
The Jackson Laboratory

Co-Authors: Wilson L, Howell G, Hartford S, Sears A, Schimenti J
Institutions: The Jackson Laboratory

With the completion of the human and mouse genomes, functional genomics will become the future of genome research. Phenotype driven studies using ENU is one of the systematic tools of genome analysis.

Our laboratory has been conducting a large scale ENU mutagenesis program designed to isolate ENU-induced recessive mutations mapping within or near the Rw inversion. The region is associated with a chromosomal inversion spanning 30 cM of the proximal region of mouse chromosome (Chr) 5.

A series of overlapping deletion complexes have been generated across the Rw region can that facilitate systematic functional analyses of the region of interest. Based on the principle of allelic noncomplementation, ENU induced mutations can be localized to the region of a deletion with a single mating pair.

G3 mice, homozygous for the ENU treated chromosome, were screened for morphological anomalies, vestibular defects, hearing loss, sterility and DNA repair defects. The screen also incorporated visible markers to allow for identification of recessive embryonic lethal mutations. To date, a total of 697 families have been screened with revealing one family with hearing abnormalities, one with craniofacial defects, one male sterility, and eighteen families showing probable embryonic lethality. Having identified heritable mutations, further studies are being initiated to identify the underlying genes and to eventually understand their functions.

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