We are investigating a fifty-year-old observation that lysine1 red cell1 (lys1 rc1) double mutants accumulate pigmented fat cells in the head and thorax of adult flies (Grell, 1961). Toward this goal, we have confirmed that lys1 rc1 mutants exhibit pigmented cells and have used GC-MS to determine that lysine levels are increased 50-fold in lys1 single mutants. These results demonstrate that the lys1 rc1 mutant phenotypes stem from a metabolic defect and implicate lysine catabolism in the development of adult adipose tissue. As a first step towards studying the molecular mechanisms that underlie these phenotypes, we used deficiency mapping to identify the genes that are disrupted by the lys1 and rc1 mutations. We have successfully used a GC-MS-based approach to map the lys1 mutation to an ~10,000 bp region of chromosome 2 that contains the gene lysine ketoglutarate reductase/saccharopine dehydrogenase (LKRSDH), which encodes an essential enzyme in lysine catabolism. Furthermore, we have determined that lys1 fails to complement LKRSDHMB10942 and have identified the causal mutation as a large insertion in the second exon of LKRSDH. We have also mapped rc based on a previous observation that rc1 single mutants accumulate pigmented fat cells if starved during the post-critical weight period of L3 development. We used this phenotype to demonstrate that rc1 is located within an ~60,000 bp region of chromosome 2 and we are now employing a whole-genome sequencing approach to identify the causal lesion. Overall, our studies suggest that degradation of the essential amino acid lysine influences the metabolism and development of adult adipose tissue.
Grell E.H. (1961). The genetics and biochemistry of red fat cells in Drosophila melanogaster. Genetics 46: 925-933.