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Journal of Neuroscience, Vol 16, 1819-1826, Copyright © 1996 by Society for Neuroscience
Cell death in the midbrain of the murine mutation weaver
S Roffler-Tarlov, B Martin, AM Graybiel and JS Kauer
Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
The midbrain of the adult homozygous weaver (wv/wv) mouse is notable for a
reduction in the numbers of dopamine-containing cells in the substantia
nigra (A9) and the retrorubral nucleus (A8). We have determined that the
reduction in tyrosine hydroxylase (TH)-positive neurons in the ventral
midbrain of the weaver is attributable to the loss of neurons after
postnatal day 7 (P7). Because the number and spatial distribution of
TH-positive mesencephalic neurons in wv/wv, heterozygous weavers (+/wv),
and wild-type mice are not significantly different on P7, we conclude that
the early developmental steps of proliferation and migration have taken
place normally in the mutant. Although numbers and distribution of cells
are normal in the wv/wv on P7, the appearance of the TH-stained ventral
midbrain is abnormal because of the paucity of TH-stained dendritic
processes. The ventrally extending TH-positive dendrites are largely absent
in the young wv/wv. The wv/wv also can be distinguished from both
homozygous normal (+/+) and wv/wv littermates on P7 based on the appearance
of dendrites that are more numerous than in the wv/wv but thin,
disorganized, and sparse compared with +/+. Most cell death seems to take
place in wv/wv before P21. However, at least one subset of
dopamine-containing neurons disappears later. The zone of densely packed
TH-positive neurons in the substantia nigra that is likely to be the origin
of innervation to striosomes in the caudoputamen disappears between P21 and
adulthood. Despite the early pathology evident in the mesencephalic
dopamine- producing neurons of the +/wv, no evidence for cell death was
observed there even in the oldest +/wv weavers studied.
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