SCA7 knockin mice model human SCA7 and reveal gradual accumulation of mutant ataxin-7 in neurons and abnormalities in short-term plasticity

Seung Yun Yoo, Mark Pennesi, Edwin J. Weeber, Bisong Xu, Richard Atkinson, Shiming Chen, Dawna L. Armstrong, Samuel M. Wu, J. David Sweatt, Huda Y. Zoghbi

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

We targeted 266 CAG repeats (a number that causes infantile-onset disease) into the mouse Sca7 locus to generate an authentic model of spinocerebellar ataxia type 7 (SCA7). These mice reproduced features of infantile SCA7 (ataxia, visual impairments, and premature death) and showed impaired short-term synaptic potentiation; downregulation of photoreceptor-specific genes, despite apparently normal CRX activity, led to shortening of photoreceptor outer segments. Wild-type ataxin-7 was barely detectable, as was mutant ataxin-7 in young animals; with increasing age, however, ataxin-7 staining became more pronounced. Neurons that appeared most vulnerable had relatively high levels of mutant ataxin-7; it is interesting, however, that marked dysfunction occurred in these neurons weeks prior to the appearance of nuclear inclusions. These data demonstrate that glutamine expansion stabilizes mutant ataxin-7, provide an explanation for selective neuronal vulnerability, and show that mutant ataxin-7 impairs posttetanic potentiation (PTP).

Original languageEnglish (US)
Pages (from-to)383-401
Number of pages19
JournalNeuron
Volume37
Issue number3
DOIs
StatePublished - Feb 6 2003
Externally publishedYes

Fingerprint

Spinocerebellar Ataxias
Neurons
Intranuclear Inclusion Bodies
Premature Mortality
Vision Disorders
Ataxia
Glutamine
Ataxin-7
Down-Regulation
Staining and Labeling
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

SCA7 knockin mice model human SCA7 and reveal gradual accumulation of mutant ataxin-7 in neurons and abnormalities in short-term plasticity. / Yoo, Seung Yun; Pennesi, Mark; Weeber, Edwin J.; Xu, Bisong; Atkinson, Richard; Chen, Shiming; Armstrong, Dawna L.; Wu, Samuel M.; Sweatt, J. David; Zoghbi, Huda Y.

In: Neuron, Vol. 37, No. 3, 06.02.2003, p. 383-401.

Research output: Contribution to journalArticle

Yoo, SY, Pennesi, M, Weeber, EJ, Xu, B, Atkinson, R, Chen, S, Armstrong, DL, Wu, SM, Sweatt, JD & Zoghbi, HY 2003, 'SCA7 knockin mice model human SCA7 and reveal gradual accumulation of mutant ataxin-7 in neurons and abnormalities in short-term plasticity', Neuron, vol. 37, no. 3, pp. 383-401. https://doi.org/10.1016/S0896-6273(02)01190-X
Yoo, Seung Yun ; Pennesi, Mark ; Weeber, Edwin J. ; Xu, Bisong ; Atkinson, Richard ; Chen, Shiming ; Armstrong, Dawna L. ; Wu, Samuel M. ; Sweatt, J. David ; Zoghbi, Huda Y. / SCA7 knockin mice model human SCA7 and reveal gradual accumulation of mutant ataxin-7 in neurons and abnormalities in short-term plasticity. In: Neuron. 2003 ; Vol. 37, No. 3. pp. 383-401.
@article{9f68c18a552640f6902df384645e6789,
title = "SCA7 knockin mice model human SCA7 and reveal gradual accumulation of mutant ataxin-7 in neurons and abnormalities in short-term plasticity",
abstract = "We targeted 266 CAG repeats (a number that causes infantile-onset disease) into the mouse Sca7 locus to generate an authentic model of spinocerebellar ataxia type 7 (SCA7). These mice reproduced features of infantile SCA7 (ataxia, visual impairments, and premature death) and showed impaired short-term synaptic potentiation; downregulation of photoreceptor-specific genes, despite apparently normal CRX activity, led to shortening of photoreceptor outer segments. Wild-type ataxin-7 was barely detectable, as was mutant ataxin-7 in young animals; with increasing age, however, ataxin-7 staining became more pronounced. Neurons that appeared most vulnerable had relatively high levels of mutant ataxin-7; it is interesting, however, that marked dysfunction occurred in these neurons weeks prior to the appearance of nuclear inclusions. These data demonstrate that glutamine expansion stabilizes mutant ataxin-7, provide an explanation for selective neuronal vulnerability, and show that mutant ataxin-7 impairs posttetanic potentiation (PTP).",
author = "Yoo, {Seung Yun} and Mark Pennesi and Weeber, {Edwin J.} and Bisong Xu and Richard Atkinson and Shiming Chen and Armstrong, {Dawna L.} and Wu, {Samuel M.} and Sweatt, {J. David} and Zoghbi, {Huda Y.}",
year = "2003",
month = "2",
day = "6",
doi = "10.1016/S0896-6273(02)01190-X",
language = "English (US)",
volume = "37",
pages = "383--401",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - SCA7 knockin mice model human SCA7 and reveal gradual accumulation of mutant ataxin-7 in neurons and abnormalities in short-term plasticity

AU - Yoo, Seung Yun

AU - Pennesi, Mark

AU - Weeber, Edwin J.

AU - Xu, Bisong

AU - Atkinson, Richard

AU - Chen, Shiming

AU - Armstrong, Dawna L.

AU - Wu, Samuel M.

AU - Sweatt, J. David

AU - Zoghbi, Huda Y.

PY - 2003/2/6

Y1 - 2003/2/6

N2 - We targeted 266 CAG repeats (a number that causes infantile-onset disease) into the mouse Sca7 locus to generate an authentic model of spinocerebellar ataxia type 7 (SCA7). These mice reproduced features of infantile SCA7 (ataxia, visual impairments, and premature death) and showed impaired short-term synaptic potentiation; downregulation of photoreceptor-specific genes, despite apparently normal CRX activity, led to shortening of photoreceptor outer segments. Wild-type ataxin-7 was barely detectable, as was mutant ataxin-7 in young animals; with increasing age, however, ataxin-7 staining became more pronounced. Neurons that appeared most vulnerable had relatively high levels of mutant ataxin-7; it is interesting, however, that marked dysfunction occurred in these neurons weeks prior to the appearance of nuclear inclusions. These data demonstrate that glutamine expansion stabilizes mutant ataxin-7, provide an explanation for selective neuronal vulnerability, and show that mutant ataxin-7 impairs posttetanic potentiation (PTP).

AB - We targeted 266 CAG repeats (a number that causes infantile-onset disease) into the mouse Sca7 locus to generate an authentic model of spinocerebellar ataxia type 7 (SCA7). These mice reproduced features of infantile SCA7 (ataxia, visual impairments, and premature death) and showed impaired short-term synaptic potentiation; downregulation of photoreceptor-specific genes, despite apparently normal CRX activity, led to shortening of photoreceptor outer segments. Wild-type ataxin-7 was barely detectable, as was mutant ataxin-7 in young animals; with increasing age, however, ataxin-7 staining became more pronounced. Neurons that appeared most vulnerable had relatively high levels of mutant ataxin-7; it is interesting, however, that marked dysfunction occurred in these neurons weeks prior to the appearance of nuclear inclusions. These data demonstrate that glutamine expansion stabilizes mutant ataxin-7, provide an explanation for selective neuronal vulnerability, and show that mutant ataxin-7 impairs posttetanic potentiation (PTP).

UR - http://www.scopus.com/inward/record.url?scp=0037421691&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037421691&partnerID=8YFLogxK

U2 - 10.1016/S0896-6273(02)01190-X

DO - 10.1016/S0896-6273(02)01190-X

M3 - Article

VL - 37

SP - 383

EP - 401

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 3

ER -