Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice - PubMed (original) (raw)

Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice

I A Klement et al. Cell. 1998.

Free article

Abstract

Transgenic mice carrying the spinocerebellar ataxia type 1 (SCA1) gene, a polyglutamine neurodegenerative disorder, develop ataxia with ataxin-1 localized to aggregates within cerebellar Purkinje cells nuclei. To examine the importance of nuclear localization and aggregation in pathogenesis, mice expressing ataxin-1[82] with a mutated NLS were established. These mice did not develop disease, demonstrating that nuclear localization is critical for pathogenesis. In a second series of transgenic mice, ataxin-1[77] containing a deletion within the self-association region was expressed within Purkinje cells nuclei. These mice developed ataxia and Purkinje cell pathology similar to the original SCA1 mice. However, no evidence of nuclear ataxin-1 aggregates was found. Thus, although nuclear localization of ataxin-1 is necessary, nuclear aggregation of ataxin-1 is not required to initiate pathogenesis in transgenic mice.

PubMed Disclaimer

Comment in

• Nuclear inclusions in glutamine repeat disorders: are they pernicious, coincidental, or beneficial?
  Sisodia SS. Sisodia SS. Cell. 1998 Oct 2;95(1):1-4. doi: 10.1016/s0092-8674(00)81743-2. Cell. 1998. PMID: 9778239 No abstract available.

Similar articles

• Progress in pathogenesis studies of spinocerebellar ataxia type 1.
  Cummings CJ, Orr HT, Zoghbi HY. Cummings CJ, et al. Philos Trans R Soc Lond B Biol Sci. 1999 Jun 29;354(1386):1079-81. doi: 10.1098/rstb.1999.0462. Philos Trans R Soc Lond B Biol Sci. 1999. PMID: 10434309 Free PMC article. Review.
• Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in SCA1 transgenic mice.
  Emamian ES, Kaytor MD, Duvick LA, Zu T, Tousey SK, Zoghbi HY, Clark HB, Orr HT. Emamian ES, et al. Neuron. 2003 May 8;38(3):375-87. doi: 10.1016/s0896-6273(03)00258-7. Neuron. 2003. PMID: 12741986
• Spinocerebellar ataxia type 1--modeling the pathogenesis of a polyglutamine neurodegenerative disorder in transgenic mice.
  Clark HB, Orr HT. Clark HB, et al. J Neuropathol Exp Neurol. 2000 Apr;59(4):265-70. doi: 10.1093/jnen/59.4.265. J Neuropathol Exp Neurol. 2000. PMID: 10759181 Review.
• Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures.
  Skinner PJ, Koshy BT, Cummings CJ, Klement IA, Helin K, Servadio A, Zoghbi HY, Orr HT. Skinner PJ, et al. Nature. 1997 Oct 30;389(6654):971-4. doi: 10.1038/40153. Nature. 1997. PMID: 9353120
• Altered trafficking of membrane proteins in purkinje cells of SCA1 transgenic mice.
  Skinner PJ, Vierra-Green CA, Clark HB, Zoghbi HY, Orr HT. Skinner PJ, et al. Am J Pathol. 2001 Sep;159(3):905-13. doi: 10.1016/S0002-9440(10)61766-X. Am J Pathol. 2001. PMID: 11549583 Free PMC article.

Cited by

• The Role of Protein Quantity Control in Polyglutamine Spinocerebellar Ataxias.
  Zhang H, Wang X. Zhang H, et al. Cerebellum. 2024 Jul 25. doi: 10.1007/s12311-024-01722-w. Online ahead of print. Cerebellum. 2024. PMID: 39052145 Review.
• Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.
  Rajan-Babu IS, Dolzhenko E, Eberle MA, Friedman JM. Rajan-Babu IS, et al. Nat Rev Genet. 2024 Jul;25(7):476-499. doi: 10.1038/s41576-024-00696-z. Epub 2024 Mar 11. Nat Rev Genet. 2024. PMID: 38467784 Review.
• Hereditary Ataxias: From Bench to Clinic, Where Do We Stand?
  Pilotto F, Del Bondio A, Puccio H. Pilotto F, et al. Cells. 2024 Feb 9;13(4):319. doi: 10.3390/cells13040319. Cells. 2024. PMID: 38391932 Free PMC article. Review.
• HD and SCA1: Tales from two 30-year journeys since gene discovery.
  Thompson LM, Orr HT. Thompson LM, et al. Neuron. 2023 Nov 15;111(22):3517-3530. doi: 10.1016/j.neuron.2023.09.036. Epub 2023 Oct 19. Neuron. 2023. PMID: 37863037 Review.
• Dysregulation of alternative splicing in spinocerebellar ataxia type 1.
  Olmos V, Thompson EN, Gogia N, Luttik K, Veeranki V, Ni L, Sim S, Chen K, Krause DS, Lim J. Olmos V, et al. Hum Mol Genet. 2024 Jan 7;33(2):138-149. doi: 10.1093/hmg/ddad170. Hum Mol Genet. 2024. PMID: 37802886 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations

• Molecular Biology Databases

  • GlyGen glycoinformatics resource
  • Mouse Genome Informatics (MGI)