RT Journal Article
SR Electronic
T1 Neurons Lacking Huntingtin Differentially Colonize Brain and Survive in Chimeric Mice
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7608
OP 7619
DO 10.1523/JNEUROSCI.21-19-07608.2001
VO 21
IS 19
A1 Anton Reiner
A1 Nobel Del Mar
A1 Christopher A. Meade
A1 Huaitao Yang
A1 Ioannis Dragatsis
A1 Scott Zeitlin
A1 Daniel Goldowitz
YR 2001
UL http://www.jneurosci.org/content/21/19/7608.abstract
AB To determine whether neurons lacking huntingtin can participate in development and survive in postnatal brain, we used two approaches in an effort to create mice consisting of wild-type cells and cells without huntingtin. In one approach, chimeras were created by aggregating the 4–8 cell embryos from matings of Hdh+/− mice with wild-type 4–8 cell embryos. No chimeric offspring that possessed homozygous Hdh−/− cells were obtained thereby, although statistical considerations suggest that such chimeras should have been created. By contrast, Hdh −/− ES cells injected into blastocysts yielded offspring that were born and in adulthood were found to have Hdh−/− neurons throughout brain. TheHdh −/− cells were, however, 5–10 times more common in hypothalamus, midbrain, and hindbrain than in telencephalon and thalamus. Chimeric animals tended to be smaller than wild-type littermates, and chimeric mice rich in Hdh−/− cells tended to show motor abnormalities. Nonetheless, no brain malformations or pathologies were evident.The apparent failure of aggregation chimeras possessing Hdh−/− cells to survive to birth is likely attributable to the previously demonstrated critical role of huntingtin in extraembryonic membranes. That Hdh−/− cells in chimeric mice created by blastocyst injection are under-represented in adult telencephalon and thalamus implies a role for huntingtin in the development of these regions, whereas the neurological dysfunction in brains enriched inHdh −/− cells suggests a role for huntingtin in adult brain. Nonetheless, the lengthy survival ofHdh −/− cells in adult chimeric mice indicates that individual neurons in many brain regions do not require huntingtin to participate in normal brain development and to survive.