International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


Oral Presentation

Monday 18 November

15:30 - 15:45 HRS

CREATING NEW MOUSE MODELS OF CARDIOVASCULAR DISEASE USING RANDOM MUTAGENESIS

S.L. Adamson
Samuel Lunenfeld Research Institute of Mount Sinai Hospital

Co-Authors: Kelsey L, Voronina I, Milenkovic Z, Whiteley J, Vukobradovic I, and others in the Centre for Modelling Human Disease.
Institutions: Samuel Lunenfeld Research Institute of Mount Sinai Hospital & University of Toronto.

Toronto’s Centre for Modelling Human Disease is creating new mouse models of human disease using random mutagenesis.  C57BL/6J male mice are injected with ethylnitrosourea (ENU) to generate mutations in sperm, then bred with normal C3H/HeJ females.  G1 offspring are screened for cardiovascular and other physiologic abnormalities. ‘Outliers’ are bred to establish heritability.  Dominant mutations responsible for traits will be localized using a genome scan.  3900 mice have undergone physiologic screening since the program began in July 2000.  Of this total, we screened 2700 for blood pressure and heart rate abnormalities using a tail cuff system, 1300 for ascending aortic blood velocity abnormalities using pulsed Doppler while under isoflurane anesthesia, and 2200 for hematologic abnormalities (hematology analyzer and blood smear).  Our ECG screen began in July 2002.To date, we have identified 25 mice with a variety of heritable defects including 6 in hematology and 2 with high ascending aortic blood velocities.  Heritability testing is underway on 41 additional outliers including 13 with cardiovascular abnormalities.  The program is always seeking new collaborators and new screening protocols.  See www.cmhd.ca for details and a list of the heritable models available.


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