Neurons lacking huntingtin differentially colonize brain and survive in chimeric mice

Anton Reiner, Nobel Del Mar, Christopher A. Meade, Huaitao Yang, Ioannis Dragatsis, Scott Zeitlin, Daniel Goldowitz

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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 wildtype 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. The Hdh -/- 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 in Hdh -/- cells suggests a role for huntingtin in adult brain. Nonetheless, the lengthy survival of Hdh -/- 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.

Original languageEnglish (US)
Pages (from-to)7608-7619
Number of pages12
JournalJournal of Neuroscience
Volume21
Issue number19
StatePublished - Oct 1 2001

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Neurons
Brain
Telencephalon
Blastocyst
Thalamus
Embryonic Structures
Extraembryonic Membranes
Rhombencephalon
Mesencephalon
Hypothalamus
Cell Survival
Parturition
Pathology
Injections

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Reiner, A., Del Mar, N., Meade, C. A., Yang, H., Dragatsis, I., Zeitlin, S., & Goldowitz, D. (2001). Neurons lacking huntingtin differentially colonize brain and survive in chimeric mice. Journal of Neuroscience, 21(19), 7608-7619.

Neurons lacking huntingtin differentially colonize brain and survive in chimeric mice. / Reiner, Anton; Del Mar, Nobel; Meade, Christopher A.; Yang, Huaitao; Dragatsis, Ioannis; Zeitlin, Scott; Goldowitz, Daniel.

In: Journal of Neuroscience, Vol. 21, No. 19, 01.10.2001, p. 7608-7619.

Research output: Contribution to journalArticle

Reiner, A, Del Mar, N, Meade, CA, Yang, H, Dragatsis, I, Zeitlin, S & Goldowitz, D 2001, 'Neurons lacking huntingtin differentially colonize brain and survive in chimeric mice', Journal of Neuroscience, vol. 21, no. 19, pp. 7608-7619.
Reiner, Anton ; Del Mar, Nobel ; Meade, Christopher A. ; Yang, Huaitao ; Dragatsis, Ioannis ; Zeitlin, Scott ; Goldowitz, Daniel. / Neurons lacking huntingtin differentially colonize brain and survive in chimeric mice. In: Journal of Neuroscience. 2001 ; Vol. 21, No. 19. pp. 7608-7619.
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