Specific genetic loci on mouse chromosome 16 (MMU16) are syntenic with genel located on human chromosome 21 (HSA21) specifically that portion of HSA21 associated with the phenotypic characteristics of Down Syndrome (DS) when present or expressed in the trisomic state (Ts21).
The specific aim of this research proposal is to utilize mice with complete trisomy of MMU16 as model systems in which to examine the embryologic consequences of this trisomy. Both mental retardation and the premature onset of dementia clinically and neuropathologically indistinguishable form senile dementia of the Alzheimer's type (SDAT) are well established deleterious effects of human (Ts21). The pathogenesis and mechanism(s) by which these neurologic effects arise are unknown. Their elucidation requires the use of an animal model system with close genetic homology. Particular emphasis in these studies will be placed upon determining the extent to which neuroanatomic features characteristic of Ts21 are present in Ts16 mice. These features include altered numbers and distributions of microneurons and altered dendritic and synaptogenetic patterns in several portions of the neuraxis. In our examination of the neuraxes of Ts16 mice and chimeras composed of Ts16 cells at successive developmental stages, we will utilize Golgi, light and electron microscopic, and immunocytochemical methods. We will focus our examinations on the cerebellar cortex, hippocampus, portions of the cerebral cortices, and the basal forebrain. The use of chimeras is critical, since Ts16 fetuses die in utero before the differentiation of the neuraxis has been completed. The completion of a neuropathogenesis study of a mammalian trisomy will serve as basis for future studies unravelling the mechanism(s) by which these morphologic abnormalities arise and may eventually serve as an assay system for ameliorative therapeutic measures.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD019932-02
Application #
3317600
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1984-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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