C. Iannicola et al., Early alterations in gene expression and cell morphology in a mouse model of Huntington's disease, J NEUROCHEM, 75(2), 2000, pp. 830-839
Several mouse models for Huntington's disease (HD) have been produced to da
te. Based on differences in strain, promoter, construct, and number of glut
amines, these models have provided a broad spectrum of neurological symptom
s, ranging from simple increases in aggressiveness with no signs of neuropa
thology, to tremors and seizures in absence of degeneration, to neurologica
l symptoms in the presence of gliosis and TUNEL (terminal deoxynucleotidyl
transferase-mediated dUTP nick end-labeling) positivity, and finally to sel
ective striatal damage associated with electrophysiological and behavioral
abnormalities. We decided to analyze the morphology of striatum and hippoca
mpus from a mouse transgenic line obtained by microinjection of exon 1 from
the HD gene after introduction of a very high number of CAG repeat units.
We found a massive darkening and compacting of striatal and hippocampal neu
rons in affected mice, associated with a lower degree of more classical apo
ptotic cell condensation. We then explored whether this morphology could be
explained with alterations in gene expression by hybridizing normal and af
fected total brain RNA to a panel of 588 known mouse cDNAs. We show that so
me genes are significantly and consistently up-regulated and that others ar
e down-regulated in the affected brains. Here we discuss the possible signi
ficance of these alterations in neuronal morphology and gene expression.