Comparative Mouse Genomics Centers Consortiun

  • Doetschman, Thomas C (PI)
  • Levin, Linda (PI)
  • Puga, Alvaro (PI)
  • Sanchez, Yolanda (PI)
  • Boivin, Gregory (PI)
  • Groden, Joanna Louise (PI)
  • Babcock, George F. (PI)
  • Aronow, Bruce J. (PI)
  • Stambrook, Peter (PI)
  • Knudsen, Erik (PI)

Project: Research project

Grant Details


DESCRIPTION (Taken from the Applicant?s Abstract)
This application proposes to produce and analyze mice that have been
engineered to express attenuated alleles of cell cycle regulatory genes. It
is anticipated that such alleles exist in human populations, but manifest
predominantly after environmental challenge. The cell cycle regulatory genes
that will be targeted are those encoding members of the Cyclin D/Cdk4, Rb,
P14ink6 complex, which plays a critical role in the passage of cells through
the G1 phase of the cell cycle. Initial emphasis will be given to a cyclin D1
polymorphism that is known to predispose to hereditary non-polyposis
colorectal cancer (HNPCC). This project will be directed by Dr. Knudsen who
is expert in the biology of Rb and the Cyclin D/Cdk4 complex. A second
project, to be directed by Dr. Yolanda Sanchez, focuses on the G2 checkpoint
and the cell cycle regulatory gene, Chkl. Dr. Sanchez?s expertise is in yeast
genetics as well as in the mechanisms governing transit of cells through G2
and M phases. Dr. Stambrook is the principal investigator of this grant and
will direct a third project that will produce mice with attenuated alleles of
the Polo kinase, Plk3. This kinase, like Chkl, has G2/M regulatory function
and is responsive to DNA damage. The University of Cincinnati College of
Medicine has made commitments to institutional core facilities, which include
a mouse Transgenic Core and a mouse knockout core. This core was established
and is directed by Dr. Tom Doetschman, who plays a key role in this proposal.
Other established cores include a DNA synthesis and sequencing core directed
by Dr. Joanna Groden, a member of our internal advisory committee, a
comparative pathology core directed by Dr. Greg Boivin, and a biostatistics
core. Three new integrated cores funded, in part, by the Howard Hughes
Medical Institute, by the Dean of the medical school, and by the Children?s
Hospital Research Foundation, are available. These include a DNA microarray
core, a proteomics core, and a bioinformatics core. This application proposes
to take advantage of these core facilities and to contribute the collective
expertise of the investigators in furthering the understanding of the
interactions between environmental challenge and variant cell cycle genes in
the genesis of disease.
Effective start/end date4/10/013/31/07


  • National Institutes of Health


  • Environmental Science(all)
  • Medicine(all)


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