Functional Annotation of Human Chromosomes 5, 16 and 19
Genes with Gene-Driven Mutagenesis in Mice.
The goal of this project is to determine the organismal function of
the genes on human chromosomes 5, 16, and 19, which were sequenced as
part of the Human Genome Project by the Joint Genome Institute.
This project, divided into five tasks, will be accomplished by analysis
of mutations generated in the ~ 1500 mouse genes that are homologs of
the human 5-16-19 genes. Top priority will be given to those
evolutionarily-conserved genes for which no functional information
currently exists. Tasks 1 (single-base-pair mutations) and 2
(constitutive knockout mutations) will generate the mutant mice,
while Tasks 3 and 4 will analyze mutant mice for obvious or subtle abnormalities.
- For Task 1, we will utilize ORNL's Cryopreserved Mutant Mouse Bank
(CMMB) of DNA, cDNA, and sperm gathered from mice mutagenized with
N-ethyl-N-nitrosourea to recover mice with single-base-pair
mutations in any target gene of interest.
- For Task 2, we will tap existing public gene-trap resources to
generate mice with germline knockout mutations.
- For Task 3, we will
- perform broad-based phenotype-screening of the new
mutant lines generated in Tasks 1 and 2 and
- disseminate this new information to the international
research community through our website
and our
Mutant Mouse Database
- For Task 4, we will use existing mouse models to determine,
at the mechanistic level, how mutations that change protein-protein,
protein-substrate, or protein-nucleic acid interactions impact the
function of protein complexes within the context of a living cell.
- For Task 5, we will establish our new
Russell Vivarium
as an internationally-known User Facility.
|
