PT - JOURNAL ARTICLE AU - Anton Reiner AU - Nobel Del Mar AU - Christopher A. Meade AU - Huaitao Yang AU - Ioannis Dragatsis AU - Scott Zeitlin AU - Daniel Goldowitz TI - Neurons Lacking Huntingtin Differentially Colonize Brain and Survive in Chimeric Mice AID - 10.1523/JNEUROSCI.21-19-07608.2001 DP - 2001 Oct 01 TA - The Journal of Neuroscience PG - 7608--7619 VI - 21 IP - 19 4099 - http://www.jneurosci.org/content/21/19/7608.short 4100 - http://www.jneurosci.org/content/21/19/7608.full SO - J. Neurosci.2001 Oct 01; 21 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.