Seattle
Comparative Mouse Genomics Center
Variationsin
the human genome commonly found within the population
may predispose affected individuals to frequently occurring
disease conditions. The existence of these DNA sequence
variations, called single nucleotide polymorphisms or
SNPs, has sparked intense interest within the scientific
community to identify and characterize them for epidemiological
study. However, the functional significance of SNP variants
in DNA repair genes in relation to environmental toxins
and carcinogens is largely unknown. The objective of
the Seattle Comparative Mouse Genomics Center
is to develop genetically engineered mouse models for
studying SNP variant-environment interactions, using
the resources and expertise found at the University
of Washington and Fred Hutchinson Cancer Research Center.
These resources include genomics, transgenic technology,
mouse genetics, bioinformatics, biostatistics, ecogenetics
and environmental health, flow cytometry, whole mouse
molecular imaging, comparative pathology, and the molecular
genetics of DNA repair/cell cycle control genes. Scientists
in the Center are developing genomic technology including
the prediction of SNP function by 3 dimensional, macromolecular
protein structure, BAC recombineering and siRNA driven
systems for gene manipulation. With the creation of
an electronic data base system to enhance communication
of unique mouse model data, all efforts are focused
on generating new biologically relevant mouse models.
Center
for Ecogenetics and Environmental Health
CEEH
strives to understand and communicate how genetic
factors influence human susceptibility to environmental
health risks. Differences in genetic make-up affect
the way we respond to environmental health risks,
such as exposure to toxic chemicals like pesticides.
CEEH scientists do basic research on the ways that
genetic and environmental factors combine to affect
susceptibility to diseases and disorders including
asthma, birth defects, cancer, Parkinson’s Disease,
other neurological disorders, and adverse reactions
to drugs and chemicals.
Transgenic
Resources Program
The
Transgenic Resource laboratory, located in the new
genetically engineered rodent facility, has been in
operation since 1995. It is supported, in part, by
two program projects from the NIA and NIEHS. It has
been highly successful in generating and developing
transgenic and gene-targeted mouse models for aging
and environmental health sciences. Full scale technologies
are available including vector and construct preparation,
random integration over-expression, ES cell technology,
knock-outs, knock-ins, point mutations, and inducible
and temporal expression systems. This is a full service
resource program providing pronuclear microinjection,
mouse embryonic stem (ES) cell technology and transgenic
colony management. The laboratory is currently generating
about 70 transgenic and gene targeted mouse lines
per year. In addition, about 80 lines are maintained
for investigators for colony expansion and intercross
or backcross breeding experiments. Our methods used
to generate transgenic and gene targeted mutant mice
have been described in detail (Ladiges and Ware, 1999).
Nathan
Shock Center of Excellence in Basic Biology of Aging
The
Shock Centerprovides resources to support the large
community of University
of Washington investigators involved in gerontology
research, including Alzheimer’s Disease and Werner’s
Syndrome.
It is comprised of three major cores: Transgenic Animal
Model Development, Flow Cytometry and Cell Sorting,
and Gene Expression.
