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Titolo:
Huntingtin is required for normal hematopoiesis
Autore:
Metzler, M; Helgason, CD; Dragatsis, I; Zhang, TQ; Gan, L; Pineault, N; Zeitlin, SO; Humphries, RK; Hayden, MR;
Indirizzi:
Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Vancouver,BC V5Z 4H4, Canada Univ British Columbia Vancouver BC Canada V5Z 4H4 uver,BC V5Z 4H4, Canada British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada British Columbia Canc Agcy Vancouver BC Canada V5Z 1L3 BC V5Z 1L3, Canada Columbia Univ, Dept Genet & Dev, Russ Berrie Ctr, New York, NY 10032 USA Columbia Univ New York NY USA 10032 ss Berrie Ctr, New York, NY 10032 USA Columbia Univ, Dept Pathol, New York, NY 10032 USA Columbia Univ New YorkNY USA 10032 , Dept Pathol, New York, NY 10032 USA Univ British Columbia, Dept Med, Vancouver, BC V5Z 4H4, Canada Univ British Columbia Vancouver BC Canada V5Z 4H4 ver, BC V5Z 4H4, Canada
Titolo Testata:
HUMAN MOLECULAR GENETICS
fascicolo: 3, volume: 9, anno: 2000,
pagine: 387 - 394
SICI:
0964-6906(20000212)9:3<387:HIRFNH>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
EMBRYONIC STEM-CELLS; SACCHAROMYCES-CEREVISIAE; WILD-TYPE; IN-VITRO; PROTEIN; DISEASE; BRAIN; INTERACTS; LETHALITY; LOCALIZATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Hayden, MR Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut,950 W 28thAve, Vancouver, BC V5Z 4H4, Canada Univ British Columbia 950 W 28th Ave Vancouver BC Canada V5Z 4H4
Citazione:
M. Metzler et al., "Huntingtin is required for normal hematopoiesis", HUM MOL GEN, 9(3), 2000, pp. 387-394

Abstract

Huntington's disease (HD) is a neurodegenerative disease associated with polyglutamine expansion in huntingtin, a widely expressed protein. The function of huntingtin is unknown although huntingtin plays a fundamental role in development since gene targeted HD-/- mouse embryos die shortly after gastrulation, Expression of huntingtin is detected in spleen and thymus but its role in hematopoiesis has not been examined. To determine the function ofhuntingtin and to provide insight into potential pathologic mechanisms in HD, we analyzed the role of huntingtin in hematopoietic development. Expression of huntingtin was analyzed in a variety of hematopoietic cell types, and in vitro hematopoiesis was assessed using an HD+/- and several HD-/- embryonic stem (ES) cell lines. Although wild-type, HD+/- and HD-/- ES cell lines formed primary embryoid bodies (EBs) with similar efficiency, the numbers of hematopoietic progenitors detected at various stages of the in vitro differentiation were reduced in HD+/- and HD-/- ES cell lines examined. Expression analyses of hematopoietic markers within the EBs revealed that primitive and definitive hematopoiesis occurs in the absence of huntingtin, However, further analysis using a suspension culture in the presence of hematopoietic cytokines demonstrated a highly significant gene dosage-dependent decrease in proliferation and/or survival of HD+/- and HD-/- cells. Enrichment for the CD34(+) cells within the EB confirmed that the impairment is intrinsic to the hematopoietic cells. These observations suggest that huntingtin expression is required for the generation and expansion of hematopoieticcells and provides an alternative system in which to assess the function of huntingtin.

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Documento generato il 30/05/20 alle ore 02:39:31