129. Using Overlapping Deletions in the Analysis of Recessive Phenotypes 

Yun You, Hanna Chao, Sarah Mentzer, Rebecca Bergstrom¹, and John Schimenti¹ 
Life Sciences Division, Oak Ridge National Laboratory, PO Box 2009, Oak Ridge, Tennessee 37831-8077 
¹The Jackson Laboratory, Bar Harbor, Maine 04609 
1yy@ornl.gov 

Chromosomal deletions have been exploited to perform a systematic characterization of functional units in Drosophila melanogaster. The Human Genome Project will generate nucleotide sequences of 10⁹ base pairs, an estimated 80,000 to 100,000 genes in human, and only a small percentage of them has a known role. As a model system, the mouse is an indispensable tool to decipher mammalian gene function. A high throughput method has recently been developed to induce chromosomal deletions at any region of the mouse genome by radiation in embryonic stem (ES) cells. Lines of mutant mice carrying deletions around the D17Aus9 locus have been generated by this strategy. Deletion analysis of mutant mice called D17Aus9^df10J carrying a small deletion showed that an early lethal gene is located near the D17Aus9 locus. Early lethality renders further deletion analysis of this region difficult. In our deletion analysis this problem was easily avoided by using Del(17)T^7J, another mutant line carrying a deletion, which does not encompass the D17Aus9 locus, but overlap with the deleted region found in D17Aus9^df10J. By crossing D17Aus9^df10J /+ to Del(17)T^7J /+, the heterozygous compound deletions unveiled a late action recessive lethal locus. The deletion analysis data and initial characterization of this lethal mutant will be presented. 

Above results illustrate the importance to generate sets of overlapping deletion complexes in the mouse chromosome 15 mutagenesis project at Oak Ridge National Laboratory (see abstract of E. Rinchik, et. al). The deletions will be used as mapping tools to locate the ENU-induced point mutations, and will also serve as reagents to identify functional units and clone genes important for mouse development along chromosome 15. 

[Research currently sponsored by USDOE, under contract DE-AC05-960R22464 with Lockheed Martin Energy Research, Inc.]