Parkinson?s disease (PD) is a common progressive neurodegenerative disease affecting approximately 2 percent of the population over age 65 throughout the world. Evidence from studies of idiopathic PD suggests that it is a complex disease involving multiple genetic and environmental factors. We have developed a potential mouse model of idiopathic Parkinson?s disease in the Engrailed-i (En-i) knockout mouse, En aboutiM. Homozygous En about ih/d mice on the 129/Sv inbred strain display severe cerebellar hypoplasia and perinatal lethality. In contrast, on the C57B1/6J inbred strain, homozygous mice are viable and exhibit tremors and hesitant gate reminiscent of Parkinson?s disease. To further analyze the role of strain background on the En-i mutant phenotype we propose the following three specific aims: 1) further characterize the Parkinson?s disease phenotype of En-i deficient mice, 2) genetically map strain-specific modifier genes required to produce the PD phenotype in En-1hd mutant mice, and 3) analyze candidate modifier genes for strain-specific alterations that contribute to the PD phenotype. The discovery of new genes with a genetic link to PD will provide future targets for therapeutic intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32NS043844-01
Application #
6487111
Study Section
Special Emphasis Panel (ZRG1-F01 (20))
Program Officer
Murphy, Diane
Project Start
2002-06-01
Project End
2005-05-31
Budget Start
2002-06-01
Budget End
2003-05-31
Support Year
1
Fiscal Year
2002
Total Cost
$38,320
Indirect Cost
Name
Case Western Reserve University
Department
Genetics
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Bilovocky, Natalie A; Romito-DiGiacomo, Rita R; Murcia, Crystal L et al. (2003) Factors in the genetic background suppress the engrailed-1 cerebellar phenotype. J Neurosci 23:5105-12