Lengthening a glutamine tract in huntingtin confers a dominant attribute that initiates degeneration of striatal neurons in Huntington’s disease (HD). To identify pathways that are candidates for the mutant protein’s abnormal function, we compared striatal cell lines established from wild-type and HdhQ111 knock-in embryos. Alternate versions of full-length huntingtin, distinguished by epitope accessibility, were localized to different sets of nuclear and perinuclear organelles involved in RNA biogenesis and membrane trafficking. However, mutant STHdhQ111 cells also exhibited additional forms of the full-length mutant protein and displayed dominant phenotypes that did not mirror phenotypes caused by either huntingtin deficiency or excess. These phenotypes indicate a disruption of striatal cell homeostasis by the mutant protein, via a mechanism that is separate from its normal activity. They also support specific stress pathways, including elevated p53, endoplasmic reticulum stress response and hypoxia, as potential players in HD.

Dominant phenotypes produces by HD mutation in StHdh111 striatal cells / Trettel, Flavia; Rigamonti, D; HILDTICH MAGUIRE, P; WHEELER V., C; SHARP A., H; Persichetti, F; Cattaneo, E. AND MACDONALD M. E.. - In: HUMAN MOLECULAR GENETICS. - ISSN 0964-6906. - STAMPA. - 9:(2000), pp. 2799-2809. [10.1093/hmg/9.19.2799]

Dominant phenotypes produces by HD mutation in StHdh111 striatal cells.

TRETTEL, Flavia;
2000

Abstract

Lengthening a glutamine tract in huntingtin confers a dominant attribute that initiates degeneration of striatal neurons in Huntington’s disease (HD). To identify pathways that are candidates for the mutant protein’s abnormal function, we compared striatal cell lines established from wild-type and HdhQ111 knock-in embryos. Alternate versions of full-length huntingtin, distinguished by epitope accessibility, were localized to different sets of nuclear and perinuclear organelles involved in RNA biogenesis and membrane trafficking. However, mutant STHdhQ111 cells also exhibited additional forms of the full-length mutant protein and displayed dominant phenotypes that did not mirror phenotypes caused by either huntingtin deficiency or excess. These phenotypes indicate a disruption of striatal cell homeostasis by the mutant protein, via a mechanism that is separate from its normal activity. They also support specific stress pathways, including elevated p53, endoplasmic reticulum stress response and hypoxia, as potential players in HD.
DISEASE GENE-PRODUCT, HUNTINGTONS-DISEASE, MUTANT HUNTINGTIN, IN-VIVO, PROTEINS, LOCALIZATION, EXPRESSION, PATHOLOGY, NUCLEAR, FAMILY
01 Pubblicazione su rivista::01a Articolo in rivista
Dominant phenotypes produces by HD mutation in StHdh111 striatal cells / Trettel, Flavia; Rigamonti, D; HILDTICH MAGUIRE, P; WHEELER V., C; SHARP A., H; Persichetti, F; Cattaneo, E. AND MACDONALD M. E.. - In: HUMAN MOLECULAR GENETICS. - ISSN 0964-6906. - STAMPA. - 9:(2000), pp. 2799-2809. [10.1093/hmg/9.19.2799]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/142040
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 275
  • Scopus 495
  • ???jsp.display-item.citation.isi??? 480
social impact