Christian Schmedt, Ph.D.
Associate Director of Genetics
While there are more than twenty thousand known genes in the genome, the vast majority are uncharacterised in the setting of an intact organism. Finding these functions is one of the main purposes of the Genetics Phenotyping Group at GNF.
We use the chemical mutagen, N-ethyl-N-nitrosourea (ENU), to induce random genome-wide point mutations that can then be identified with our high-throughput genotyping tools. The power of the ENU approach is the wide range of mutations it can induce—not just null mutations, but hypomorphs, dominant negatives, and others. ENU allows for an unbiased, genome-wide survey of gene function. At GNF we are able to test for phenotypes in disease areas including immunology, neurobiology, vision, metabolic disorders, and hearing.
Using the latest technology, we have established a high throughput phenotyping core capable of hundreds of screens per day in a state-of-the-art, 7,000-UNIT, pathogen free barrier facility. Current screening protocols include flow cytometry, hematology, blood chemistry, body fat composition by NMR, disorders of the eye, locomotor activity, acoustic startle and prepulse inhibition, and fear conditioning. We also study measures of anxiety and depression such as the light/dark and elevated plus maze assays, stress-induced hyperthermia and the forced swim and tail suspension tests. We have developed and validated a number of secondary assays including blood pressure, auditory brainstem response, and restraint stress.
Working in close collaboration with our genotyping group, we have cloned over 40 ENU mutants. These include strains which are resistant to pathological increases in fat mass despite being fed a high calorie, fat-laden diet and other strains which have unusually low levels of cholesterol. Identification of the genetic lesions in these strains have improved our understanding of human type II diabetes and the metabolic syndrome. In a separate genetic screen, we have identified several strains which have attenuated immune responses, suggesting new strategies for increasing the success of organ transplants.
Selected Publications
- Ching KA, Cooke MP, Tarantino LM, Lapp H. Data and animal management software for large-scale phenotype screening. Mamm Genome 2006;17(4):288-97.
- Reijmers LG, Coats JK, Pletcher MT, Wiltshire T, Tarantino LM, Mayford M. A mutant mouse with a highly specific contextual fear-conditioning deficit found in an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. Learn Mem 2006;13(2):143-9.
Please click here for a full list of group publications
