Project: Research project

Project Details


The weaver (wv) mutant mouse, the only known rodent model characterized by
the association of a genetically determined degeneration of the neurons of
the substantia nigra (SN) and of the cerebellar granule cells, lends itself
to an analysis of fundamental issues of pathologic neurobiology which are
relevant to the understanding of human neurodegenerative disorders. The
strength of the proposal has been built from established work of each of
the investigators who possess diverse backgrounds representing the fields
of neuropathology and neuromorphology, developmental neurobiology,
neurochemistry and pharmacology, molecular biology and genetics. The
investigators are united by a common goal, i.e. understanding the
mechanisms of nerve cell degeneration in the nigrostriatal system damaged
by the genetic mutation. The cohesive effort is organized in a multi-
disciplinary and highly interactive research program. We plan to
investigate: the neuropathologic alterations of the nigrostriatal system
using morphometric quantitative approaches combined with new developmental
and genetic strategies; the transmitter neurochemistry of the SN and the
molecular biological mechanisms which underlie the wv defect. Project #1 will investigate the influences of the strain associated
variability of the number of midbrain dopamine neurons upon the expression
of a single gene mutation affecting that neuronal population. Project #2
will characterize the embryogenesis of the SN and the postnatal
degeneration of both the SN and striatum of the wv mutant. Project #3
plans to investigate the functional neurochemical correlates of the SN
deficit and to study the adaptive changes which take place when various
neuronal systems attempt to compensate for the deleterious effect of the
mutation. Project #4 is directed to isolate and characterize the weaver
gene and to study its expression during development.
Effective start/end date1/1/9112/31/98


  • National Institutes of Health
  • National Institutes of Health: $907,103.00
  • National Institutes of Health: $851,246.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $805,071.00
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)
  • Neuroscience(all)

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