Skip to main content
SpringerLink
Log in

Wild-type huntingtin plays a role in brain development and neuronal survival

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

While the role of the mutated Huntington’s disease (HD) protein in the pathogenesis of HD has been the focus of intensive investigation, the normal protein has received less attention. Nonetheless, the wild-type HD protein appears to be essential for embryogenesis, since deletion of the HD gene in mice results in early embryonic lethality. This early lethality is due to a critical role the HD protein, called huntingtin (Htt), plays in extraembryonic membrane function, presumably in vesicular transport of nutrients. Studies of mutant mice expressing low levels of Htt and of chimeric mice generated by blastocyst injection of Hdh-/- embryonic stem cells show that wild-type Htt plays an important role later in development as well, specifically in forebrain formation. Moreover, various lines of study suggest that normal Htt is also critical for survival of neurons in the adult forebrain.

The observation that Htt plays its key developmental and survival roles in those brain areas most affected in HD raises the possibility that a subtle loss of function on the part of the mutant protein or a sequestering of wild-type Htt by mutant Htt may contribute to HD pathogenesis. Regardless of whether this is so, the prosurvival role of Htt suggests that HD therapies that block production of both wild-type and mutant Htt may themselves be harmful.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Albin R. L. and Tagle D. A. (1995) Genetics and molecular biology of HD. Trends Neurosci. 18, 11–14.

    Article  PubMed  CAS  Google Scholar 

  • Altar C. A., Cai N., Bliven T., et al. (1997) Anterograde transport of brain-derived neurotrophic factor and its role in the brain. Nature 389, 856–860.

    Article  PubMed  CAS  Google Scholar 

  • Ambrose C. M., Duyao M. P., Barnes G., et al. (1994) Evidence against simple inactivation due to an expanded CAG repeat. Somat. Cell Molec. Genet. 20, 27–38.

    Article  PubMed  CAS  Google Scholar 

  • Aronin N., Kim M., Laforet G., and DiFiglia M. (1999) Are there multiple pathways in the pathogenesis of Huntington’s disease? Phil. Trans. R. Soc. Lond. B. 354, 995–1003.

    Article  CAS  Google Scholar 

  • Auerbach W., Hurlbert M. S., Hilditsch-Maguire P., et al. (2001) The HD mutation causes progressive neurological disease in mice expressing reduced levels of huntingtin. Hum. Mol. Gen. 10, 2515–2523.

    Article  PubMed  CAS  Google Scholar 

  • Bence N. F., Sampat R. M., and Kopito R. R. (2001) Impairment of the ubiquitin-proteosome system by protein aggregation. Science 292, 1552–1555.

    Article  PubMed  CAS  Google Scholar 

  • Bhide P. G., Day M., Sapp E., et al. (1996) Expression of normal and mutant Huntingtin in the developing brain. J. Neurosci. 16, 5523–5535.

    PubMed  CAS  Google Scholar 

  • Bruyn G. W. and Went L. N. (1986) Huntington’s chorea, In Handbook of Clinical Neurology, vol. 49 Extrapyramidal Disorders, revised series 5 (Vinken P. J., Bruyn G. W., and Klawans H. L., eds.) Elsevier Science Publishers, Amsterdam, Netherlands, pp. 267–313.

    Google Scholar 

  • Cattaneo E. Rigamonti D. Goffredo D. Zuccato C. Squitieri F., and Sipione S. (2001) Loss of normal huntingtin function: new developments in Huntington’s disease research. Trends Neurosci. 24, 182–188.

    Article  PubMed  CAS  Google Scholar 

  • Cha J. H., Kosinski C. M., Kerner J. A., et al. (1998) Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc. Natl. Acad. Sci. USA 95, 6480–6485.

    Article  PubMed  CAS  Google Scholar 

  • Chai Y., Koppenhafer S. L., Shoesmith S. J., Perez M. K., and Paulson H. L. (1999) Evidence for proteasome involvement in polyglutamine disease: localization to nuclear inclusions in SCA3/MJD and suppression of polyglutamine aggregation in vitro. Hum. Mol. Genet. 8, 673–682.

    Article  PubMed  CAS  Google Scholar 

  • Conneally P. M. (1984) Huntington Disease: Genetics and epidemiology. Am. J. Hum. Genet. 36, 506–526.

    PubMed  CAS  Google Scholar 

  • Davies S. W., Turmaine M., Cozens B. A., et al. (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90, 537–548.

    Article  PubMed  CAS  Google Scholar 

  • De La Monte S. M., Vonsattel J. P., and Richardson E. P. Jr. (1988) Morphometric demonstrations of atrophic changes in the cerebral cortex, white matter, and neostriatum in Huntington’s disease. J. Neuropathol. Exp. Neurol. 44, 516–525.

    Google Scholar 

  • DiFiglia M., Sapp E., Chase K., et al. (1995) Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron 14, 1075–1081.

    Article  PubMed  CAS  Google Scholar 

  • DiFiglia M., Sapp E., Chase K. O., Davies S. W., Bates G. P., Vonsattel J. P., and Aronin J. P. (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277, 1990–1993.

    Article  PubMed  CAS  Google Scholar 

  • Dorsman J. C., Smoor M. A., Maat-Schieman M. L. C., et al. (1999) Analysis of the subcellular localization of huntingtin with a set of rabbit polyclonal antibodies in cultured mammalian cells of neuronal origin: comparison with distribution of huntingtin in Huntington’s disease autopsy brain. Phil. Trans. R. Soc. Lond. 354, 1061–1067.

    Article  CAS  Google Scholar 

  • Dragatsis I., Efstratiadis A., and Zeitlin S. (1998) Mouse mutant embryos lacking huntingtin are rescued from lethality by wild-type extraembryonic tissues. Development 125, 1529–1539.

    PubMed  CAS  Google Scholar 

  • Dragatsis I., Levine M., and Zeitlin S. (2000) Inactivation of the mouse Huntington’s disease gene in the brain and testis results in progressive neurodegeneration and sterility. Nature Genet. 26, 300–306.

    Article  PubMed  CAS  Google Scholar 

  • Dragatsis I. and Zeitlin S. (2000) CaMKllalpha-Cre transgene expression and recombination patterns in the mouse brain. Genesis 26, 133–135.

    Article  PubMed  CAS  Google Scholar 

  • Duyao M. P., Auerbach A. B., Ryan A., et al. (1995) Inactivation of the mouse HD gene homolog Hdh. Science 269, 407–410.

    Article  PubMed  CAS  Google Scholar 

  • Fusco F. R., Chen Q., Lamoreaux W. J., et al. (1999) Cellular localization of huntingtin in striatal and cortical neurons in rats: Lack of correlation with neuronal vulnerability in Huntington’s disease. J. Neurosci. 19, 1189–1202.

    PubMed  CAS  Google Scholar 

  • Gervais F. G., Singaraja R., Xanthoudakis S., et al. (2002) Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi. Nature Cell Biol. 4, 95–105.

    Article  PubMed  CAS  Google Scholar 

  • Gusella J. F. and MacDonald M. E. (1996) Trinucleotide instability: A repeating theme in human inherited disorders. Ann. Rev. Med. 47, 201–209.

    Article  PubMed  CAS  Google Scholar 

  • Gutekunst C. A., Levey A. I., Heilman C. J., et al. (1995) Identification and localization of huntigtin in brain and hman lymphoblastoid cell lines with anti-fusion protein antibodies. Proc. Natl. Acad. Sci. USA 92, 8710–8714.

    Article  PubMed  CAS  Google Scholar 

  • Gutekunst C. A., Li S. H., Yi H., et al. (1999) Nuclear and neuropil aggregates in Huntington’s disease: relationship to neuropathology. J. Neurosci. 19, 2522–2534.

    PubMed  CAS  Google Scholar 

  • Hackam A. S., Wellington C. L., and Hayden M. R. (1998) The fatal attraction of polyglutamine-containing proteins. Clin. Gen. 53, 233–242.

    Article  CAS  Google Scholar 

  • Hackam A. S., Yassa A. S., Singaraja R., et al. (2000) Huntingtin interacting protein 1 induces apoptosis via novel caspase-dependent death effector domain. J. Biol. Chem. 275, 41,299–41,308.

    Article  CAS  Google Scholar 

  • Hebb M. O., Denovan-Wright E. M., and Robertson H. A. (1999) Expression of the Huntinton’s disease gene is regulated in astrocytes in the arcuate nucleus of the hypothalamus of postpartum rats. FASEB 9, 1099–1106.

    Google Scholar 

  • Hedreen J. C., Peyser C. E., Folstein S. E., and Ross C. A. (1991) Neuronal loss in layers V and VI of cerebral cortex in Huntington’s disease. Neurosci. Lett. 133, 257–261.

    Article  PubMed  CAS  Google Scholar 

  • Hodgson J. G., Agopyan N., Gutekunst C. A., et al. (1999) A YAC mouse model for Huntington’s disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 23, 181–192.

    Article  PubMed  CAS  Google Scholar 

  • Huntington’s Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on the HD chromosome. Cell 72, 971–983.

    Article  Google Scholar 

  • Lvkovic S. and Ehrlich M. E. (1999) Expression of the striatal DARPP-32/ARPP-21 phenotype in GABAergic neurons requires neurotrophins in vivo and in vitro. J. Neurosci. 19, 5409–5419.

    Google Scholar 

  • Kalchman M. A., Koide H. B., McCutcheon K., et al. (1997) HIP1: A human homologue of S. cerevisiae sla2p interacts with membrane-associated huntingtin in the brain. Nat. Genet. 16, 44–53.

    Article  PubMed  CAS  Google Scholar 

  • Kegel K. B., Kim M., Sapp E., McIntyre C., Castano J. G., Aronin N., and DiFiglia M. (2000) Huntingtin expression stimulates endosomal-lysosomal activity, endosome tubulation, and autophagy. J. Neurosci. 20, 7268–7278.

    PubMed  CAS  Google Scholar 

  • Kegel K. B., Meloni A. R., Yi Y., et al. (2002) Huntingtin is present in the nucleus, interacts with the transcriptional corepressor C-terminal binding protein, and represses transcription. J. Biol. Chem. 277, 7466–7476.

    Article  PubMed  CAS  Google Scholar 

  • Kim T. W. and Tanzi R. E. (1998) Neuronal intranuclear inclusions in polyglutamine diseases: nuclear weapons or nuclear fallout. Neuron 21, 657–659.

    Article  PubMed  CAS  Google Scholar 

  • Ko J., Ou S., and Patterson P. H. (2001) New antihuntingtin monoclonal antibodies: Implications for huntingtin conformation and its binding proteins. Brain Res. Bull. 56, 319–329.

    Article  PubMed  CAS  Google Scholar 

  • Landwehrmeyer G. B., McNeil S. M., Dure IV L. S., et al. (1995) HD gene: regional and cellular expression in brain of normal and affected individuals. Ann. Neurol. 37, 218–230.

    Article  PubMed  CAS  Google Scholar 

  • Leavitt B. R., Guttman J. A., Hodgson J. G., et al. (2001) Wild-type huntingtin reduces the cellular toxicity of mutant huntingtin in vivo. Am. J. Hum. Genet. 68, 313–324.

    Article  PubMed  CAS  Google Scholar 

  • Li S. H. and Li X. J. (1998) Aggregation of N-terminal huntingtin is dependent on the length of its glutamine repeats. Human Mol. Gen. 7, 801–806.

    Article  Google Scholar 

  • Li S. H., Schilling G., Young W. S. III, et al. (1993) HD gene (IT15) is widely expressed in human and rat tissues. Neuron 11, 985–993.

    Article  PubMed  CAS  Google Scholar 

  • Luthi-Carter R., Hanson S., Strand A. D., et al. (2002) Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain. Human Mol. Genet. 11, 1911–1926.

    Article  CAS  Google Scholar 

  • Maat-Schieman M. L. C., Dorsman J. C., Smoor M. A., et al. (1999) Distribution of inclusions in neuronal nuclei and dystrophic neurites in Huntington’s disease brain. J. Neuropath. Exp. Neurol. 58, 129–137.

    Article  PubMed  CAS  Google Scholar 

  • Martindale D., Hackam A., Wieczorek A., et al. (1998) Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates. Nature Gen. 18, 150–154.

    Article  CAS  Google Scholar 

  • Mehler M. F. and Gokhan S. (2000) Mechanisms underlying neural cell death in neurodegenerative diseases: alterations of a developmentally mediated cellular rheostat. Trends Neurosci. 23, 599–605.

    Article  PubMed  CAS  Google Scholar 

  • Mehler M. F. and Gokhan S. (2001) Developmental mechanisms in the pathogenesis of neurodegenerative diseases. Prog. Neurobiol. 63, 337–363.

    Article  PubMed  CAS  Google Scholar 

  • Metzler M., Chen N., Helgason C. D., et al. (1999) Life without huntingtin: Normal differentiation into functional neurons. J. Neurochem. 72, 1009–1018.

    Article  PubMed  CAS  Google Scholar 

  • Moens C. B., Cordes S. P., Giorgianni M. W., Barsh G. S., and Kimmel C. B. (1998) Equivalence in the genetic control of hindbrain segmentation in fish and mouse. Development 125, 381–391.

    PubMed  CAS  Google Scholar 

  • Myers R. H., Leavitt J., Farrer L. A., et al. (1989) Homozygote for Huntington’s Disease. Am. J. Hum. Genet. 45, 615–618.

    PubMed  CAS  Google Scholar 

  • Narain Y., Wyttenbach A., Rankin J., Furlong R. A., and Rubinsztein D. C. (1999) A molecular investigation of true dominance in Huntington’s disease. J. Med. Genet. 36, 739–746.

    PubMed  CAS  Google Scholar 

  • Nasir J., Floresco S. B., O’Kusky J. R., et al. (1995) Targeted disruption of the HD gene results in embryonic lethality and behavioral and morphological changes in heterozygotes. Cell 81, 811–823.

    Article  PubMed  CAS  Google Scholar 

  • Nucifora F. C. Jr., Sasaki M., Peters M. F., et al. (2001) Interference by huntingtin and atrophin-1 with CBP-mediated transcription leading to cellular toxicity. Science 291, 2423–2428.

    Article  PubMed  CAS  Google Scholar 

  • Ona V. O., Li M., Vonsattel J. P., et al. (1999) Inhibition of caspase-1 slows disease progression in a mouse model of Huntington’s disease. Nature 399, 263–267.

    Article  PubMed  CAS  Google Scholar 

  • Persichetti F., Carlee L., Faber P. W., et al. (1996) Differential expression of normal and mutant Huntington’s disease gene alleles. Neurobiol. Dis. 3, 183–190.

    Article  PubMed  CAS  Google Scholar 

  • Petersén Å., Larsen K. E., Behr G. G., Romero N., Przedborski S., Brundin P., and Sulzer D. (2001) Expanded CAG repeats in exon 1 of the Huntington’s disease gene stimulate dopamine-mediated striatal neuron autophagy and degeneration. Hum. Mol. Genet. 10, 1243–1254.

    Article  PubMed  Google Scholar 

  • Preisinger E., Jordan B. M., Kazantsev A., and Housman D. (1999) Evidence for a recruitment and sequestration mechanism in Huntinton’s disease. Phil. Trans. Royal Soc. Lond. 354, 1029–1034.

    Article  CAS  Google Scholar 

  • Reiner A., Del Mar N., Meade C. A., Yang H., Dragatsis I., Zeitlin S., and Goldowitz D. (2001) Neurons lacking huntingtin differentially colonize brain and survive in chimeric mice. J. Neurosci. 21, 7608–7618.

    PubMed  CAS  Google Scholar 

  • Rigamonti D., Bauer J. H., De-Fraja C., et al. (2000) Wild-type huntingtin protects from apoptosis upstream of caspase-3. J. Neurosci. 20, 3705–3713.

    PubMed  CAS  Google Scholar 

  • Rigamonti D., Sipione S., Goffredo D., Zuccato C., Fossale E., and Cattaneo E. (2001) Huntingtin’s neuroprotective activity occurs via inhibition of procaspase-9 processing. J. Biol. Chem. 276, 14,545–14,548.

    Article  CAS  Google Scholar 

  • Roos R. A. C. (1986) Neuropathology of Huntington’s Chorea, In: Handbook of Clinical Neurology, vol. 49 Extrapyramidal Disorders, revised series 5 (Vinken P. J., Bruyn G. W., and Klawans H. L., eds.) Elsevier Science Publishers, Amsterdam, Netherlands, pp. 315–326.

    Google Scholar 

  • Rosas H. D., Liu A. K., Hersch S., et al. (2002) Regional and progressive thinning of the cortical ribbon in Huntington’s disease. Neurology 58, 695–701.

    PubMed  CAS  Google Scholar 

  • Ross C. A. (2002) Polyglutamine pathogenesis: emergence of unifying mechanisms for Huntington’s disease and related disorders. Neuron 35, 819–822.

    Article  PubMed  CAS  Google Scholar 

  • Ross C. A., Margolis R. L., Belcher M. W., Wood J. D., Engelender S., and Sharp A. H. (1998) Pathogenesis of polyglutamine neurodegenerative diseases: Toward a unifying hypothesis, In: Genetic Instabilities and Hereditary Neurological Disease (Wells R., ed.) Academic Press, New York, pp. 761–776.

    Google Scholar 

  • Sanchez I., Xu C. J., Juo P., Kakizaka A., Bienis J., and Yuan J. (1999) Caspase-8 is required for cell death induced by expanded polyglutamine repeats. Neuron 22, 623–633.

    Article  PubMed  CAS  Google Scholar 

  • Sapp E., Schwarz C., Chase K., et al. (1997) Huntingtin localization in brains of normal and HD patients. Ann. Neurol. 42, 604–612.

    Article  PubMed  CAS  Google Scholar 

  • Saudou F., Finkbeiner S., Devys D., and Greenberg M. E. (1998) Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell 95, 55–66.

    Article  PubMed  CAS  Google Scholar 

  • Schilling G., Sharp A. H., Loev S. J., Wagster M. V., Li S. H., Stine O. C., and Ross C. A. (1995) Expression of the Huntington’s disease (IT15) protein product in HD patients. Human Molec. Gen. 4, 1365–1371.

    Article  CAS  Google Scholar 

  • Schuman E. M. (1999) Neurotrophin regulation of synaptic transmission. Curr. Opin. Neurobiol. 9, 105–109.

    Article  PubMed  CAS  Google Scholar 

  • Sharp A. H. and Ross C. A. (1996) Neurobiology of Huntington’s Disease. Neurobiol. Dis. 3, 3–15.

    Article  PubMed  CAS  Google Scholar 

  • Sharp A. H., Loev S. J., Schilling G., et al. (1995) Widespread expression of HD gene (IT15) protein product. Neuron 14, 1065–1074.

    Article  PubMed  CAS  Google Scholar 

  • Shieh P. B., Hu S. C., Bobb K., Timmusk T., and Ghosh A. (1998) Identification of a signaling pathway involved in calcium regulation of BDNF expression. Neuron 20, 727–740.

    Article  PubMed  CAS  Google Scholar 

  • Sisodia S. S. (1998) Nuclear inclusion in glutamine repeat disorders: Are they pernicious, coincidental or beneficial? Cell 95, 1–4.

    Article  PubMed  CAS  Google Scholar 

  • Squitieri F., Gellera C., Cannella M., et al. (2003) Homozygosity for CAG mutation in Huntington disease is associated with a more severe clinical course. Brain 126, 946–955.

    Article  PubMed  Google Scholar 

  • Storey E., Kowall N. W., Finn S. F., Mazurek M. F., and Beal M. F. (1992) The cortical lesion of Huntington’s disease: further neurochemical characterization and reproduction of some of the histological and neurochemical features by n-Methyl-d-Aspartate. Ann. Neurol. 32, 526–534.

    Article  PubMed  CAS  Google Scholar 

  • Strong T. V., Tagle D. A., Valdes J. M., et al. (1993) Widespread expression of the human and rat Huntington’s disease gene in brain and non-neural tissues. Nat. Genet. 5, 259–265.

    Article  PubMed  CAS  Google Scholar 

  • Tao X., Finkbeiner S., Arnold D. B., Shaywitz A., and Greenberg M. E. (1998) Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 20, 709–726.

    Article  PubMed  CAS  Google Scholar 

  • Velier J., Kim M., Schwarz C., Kim T. W., Sapp E., Chase K., Aronin N., and DiFiglia M. (1998) Wild-type and mutant huntingtins function in vesicle trafficking in the secretory and endocytotic pathways. Exp. Neurol. 152, 34–40.

    Article  PubMed  CAS  Google Scholar 

  • Vonsattel J. P. and DiFiglia M. (1998) Huntington Disease. J. Neuropathol. Exp. Neurol. 57, 369–384.

    PubMed  CAS  Google Scholar 

  • Vonsattel J. P., Myers R. H., Stevens T. J., Ferrante R. J., Bird E. D., and Richardson E. P. (1985) Neuropathological classification of Huntington’s disease. J. Neuropathol. Exp. Neurol. 44, 559–577.

    PubMed  CAS  Google Scholar 

  • Wexler N. S., Young A. B., Tanzi R. E., et al. (1987) Homozygotes for Huntington’s Disease. Nature 326, 194–197.

    Article  PubMed  CAS  Google Scholar 

  • Wheeler V. C., White J. K., Gutekunst C. A., et al. (2000) Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice. Hum. Mol. Genet. 9, 503–513.

    Article  PubMed  CAS  Google Scholar 

  • White J. K., Auerbach W., Duyao M. P., Vonsattel J. P., Gusella J. F., Joyner A. L., and MacDonald M. E. (1997) Huntingtin is required for neurogenesis and is not impaired by the Huntington’s disease CAG expansion. Nature Genet. 17, 404–410.

    Article  PubMed  CAS  Google Scholar 

  • Wilkinson F. L., Man N. T., Manilal S. B., Thomas P., Neal J. W., Harper P. S., Jones A. L., and Morris G. E. (1999) Localization of rabbit huntingtin using a new panel of monoclonal antibodies. Mol. Brain Res. 69, 10–20.

    Article  PubMed  CAS  Google Scholar 

  • Wilson R. S., Como P. G., Garron D. C., Klawans H. L., Barr A., and Klawans D. (1987) Memory failure in Huntington’s disease. J. Clin. Exp. Neuropsychol. 9, 147–154.

    PubMed  CAS  Google Scholar 

  • Wood J. D., McLaughlin J. C., Harper P. S., Lowenstein P. R., and Jones A. L. (1996) Partial characterization of murine huntingtin and apparent variations in the subcellular localization of huntingtin in human, mouse and rat brain. Hum. Molec. Genet. 5, 481–487.

    Article  PubMed  CAS  Google Scholar 

  • Zeitlin S., Liu J. P., Chapman D. L., Papaioannou V. E., and Efstratiadis A. (1995) Increased apoptosis and early embryonic lethality in mice nullizygous for the HD gene homologue. Nature Genet. 11, 155–163.

    Article  PubMed  CAS  Google Scholar 

  • Zeron M. M., Hansson O., Chen N., Wellington C. L., Leavitt B. R., Brundin P., Hayden M. R., and Raymond L. A. (2002) Increased sensitivity to n-methyl-d-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington’s disease. Neuron 33, 849–860.

    Article  PubMed  CAS  Google Scholar 

  • Zuccato C., Ciammola A., Rigamonti D., et al. (2001) Loss of huntingtin-mediated BDNF gene transcription in Huntington’s disease. Science 293, 493–498.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy and Neurobiology, The University of Tennessee, The Health Science Center, 38163, Memphis, TN

    Anton Reiner & Daniel Goldowitz

  2. Department of Physiology, College of Medicine, The University of Tennessee, The Health Science Center, 38163, Memphis, TN

    Ioannis Dragatsis

  3. Department of Neuroscience, University of Virginia School of Medicine, 22908, Charlottesville, VA

    Scott Zeitlin

Authors
  1. Anton Reiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ioannis Dragatsis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Scott Zeitlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniel Goldowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anton Reiner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reiner, A., Dragatsis, I., Zeitlin, S. et al. Wild-type huntingtin plays a role in brain development and neuronal survival. Mol Neurobiol 28, 259–275 (2003). https://doi.org/10.1385/MN:28:3:259

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/MN:28:3:259

Index Entries

Search

Navigation