- The Collaborative Cross,
a community resource for the genetic analysis of complex traits.
Nature Genetics, Volume 36.
The Collaborative Cross is a randomized cross of eight inbred mouse strains
designed by members of the Complex Trait Consortium. Oak Ridge National
Laboratory is the North American site of the collaborative cross, designed
to be the ultimate mouse reference population. The cross features a
randomized assortment of 8 inbred strains. The lines are first crossed pairwise
to make all 56 possible G1 parents. A set of possible 4-way crosses is
performed, keeping Y-chromosome and mitochondrial balance. Finally, all 8
genomes are brought together in G2:F1, and the offspring of this cross are
inbred. Ninety percent inbreeding is expected at G2:F20 based on
theoretical results.
- Genetics of Neuropathic and Inflammatory Hypersensitivity
In an associated project "Genetics of Neuropathic and Inflammatory
Hypersensitivity", visiting scientist William R. Lariviere of UPMC and
Co-PI Elissa Chesler at ORNL are examining multi-dimensional variation
in mechanical senisitivity and nociception followign inflammatory
stimuli. This research is supported by NIH/NIDA R01DA021198 to WRL.
- Ontological Discovery For Alcohol Research
Ontological Discovery For Alcohol Research (Chesler, PI) is an
informatics project of the Integrative Neuroscience Initiative on
Alcoholism. The project is to develop a tool for the integration of
genome and phenome through the integration and classification of
phenotype associated gene sets. http://ontologicaldiscovery.org ODE is
supported by the NIAAA Integrative Neuroscience Initiative on Alcoholism
(U01AA13499, U24AA13513).
- Cryopreserved Mutant Mouse Bank
We have generated chemically-induced point mutations for genes that are predicted
to be important in a variety of biological pathways such as: immune response,
behavior (learning, memory and drug dependence), intracellular transport and trafficking of
proteins, skeletal development and imprinting. We have targeted selected mouse genes
with homologues in human chromosomes 5, 16 and 19 and contain protein domains that
are highly conserved across distantly related genomes. Please see Efficient
gene-driven germ-line point mutagenesis of C57Bl/6 mice. BMC Genomics, volume 21,
issue 6, pg 164 2005
- Systems Biology of the Mammalian Cilium:
A Cellular Organelle Essential for Human Health and Development.
A Systems Biology approach is being applied to understand cilia function in human
health and disease. Mouse mutations for genes that are predicted to be essential
in cilia assembly and function are being generated and then phenotyped at the
molecular, cellular and whole-animal levels. This project is in collaboration with
experts in cilia structure and function at the University of Alabama
at Birmingham.
- Elucidating the Role of the Nell1
gene in Osteoblast and Chrondrocyte Differentiation
during Skull and Vertebral Column Development.
We are currently determining the molecular and cellular mechanisms mediated
by Nell1, a protein kinase C beta 1-binding protein
that is important in the formation of bone and cartilage during fetal development.
Mice with loss-of-function mutations in the
Nell1
gene exhibit skeletal defects in the skull, vertebral column and ribcage.
- Genetic variation in the health outcome
of exposure
to low doses of ionizing radiation
The detrimental effects of high doses of radiation are well-known, but the
physiological consequences of lower doses are poorly defined. Standard and recombinant
inbred strains of mice are used to dissect robust responses to low dose exposures
from those that depend on genetic background. Transcriptome profiling
is combined with functional responses and pathway mining tools to identify the molecular
mechanisms that underlie low dose radiation effects.
- Interactions between an obesigenic environment and the renin-angiotensin system.
Adipose tissue produces an increasing repertoire of adipokines with both local and systemic actions.
Levels of many of these factors are modulated by diet and energy balance. Mouse models of altered
production of one such adipokine, angiotensin II, are used to probe the extent to which adipose tissue
directly contributes to conditions that are co-morbid with obesity, such as type II diabetes.
- Health effects of inhaled nanoparticles.
Nanoparticles are both manufactured for their own value in a growing range of applications and
produced as byproducts of manufacturing processes. Despite their rapidly increasing use, the health
effects of inhaled nanoparticles have not been well-characterized. Mouse models are used to explore
the potential consequences of exposure to a variety of types of engineered particles
of nano scale.
