This project will characterize genetic loci involved in fetal-onset hydrocephalus in two rat models, through a combination of genome scanning and classic linkage analysis. The study will use two unrelated rat strains, H-Tx and LEW/Jms. Each develops hydrocephalus at 18 days of gestation (a stage equivalent to 20 weeks gestation in humans). H-Tx has a complex pattern of inheritance, whereas LEW/Jms has a simple autosomal recessive mode of inheritance. Preliminary data have identified hydrocephalus-linked loci on chromosomes 11 and 17. Fine mapping will be used to further narrow these regions of interest, and other putative regions to be identified by all-genome scanning. A congenic breeding strategy will be used to further narrow critical regions and assess the relative contribution of the loci to the phenotype. Reducing the genomic intervals will ultimately lead to positional cloning of novel genes or identification of previously mapped candidate genes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS040359-01
Application #
6167780
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Spinella, Giovanna M
Project Start
2000-09-01
Project End
2003-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
1
Fiscal Year
2000
Total Cost
$177,196
Indirect Cost
Name
University of Florida
Department
Pharmacology
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Jones, Hazel C; Chen, Gin-Fu; Yehia, Baligh R et al. (2005) Single and multiple congenic strains for hydrocephalus in the H-Tx rat. Mamm Genome 16:251-61
Somera, K C; Jones, H C (2004) Reduced subcommissural organ glycoprotein immunoreactivity precedes aqueduct closure and ventricular dilatation in H-Tx rat hydrocephalus. Cell Tissue Res 315:361-73
Jones, Hazel C; Yehia, Baligh; Chen, Gin-Fu et al. (2004) Genetic analysis of inherited hydrocephalus in a rat model. Exp Neurol 190:79-90
Jones, Hazel C; Carter, Barbara J; Morel, Laurence (2003) Characteristics of hydrocephalus expression in the LEW/Jms rat strain with inherited disease. Childs Nerv Syst 19:11-8
Jones, Hazel C; Depelteau, Jamie S; Carter, Barbara J et al. (2002) The frequency of inherited hydrocephalus is influenced by intrauterine factors in H-Tx rats. Exp Neurol 176:213-20
Jones, H C; Carter, B J; Depelteau, J S et al. (2001) Chromosomal linkage associated with disease severity in the hydrocephalic H-Tx rat. Behav Genet 31:101-11