Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription factor

Chengzu Long; Chad E Grueter; Kunhua Song; Song Qin; Xiaoxia Qi; Y Megan Kong; John M Shelton; James A Richardson; Chun-Li Zhang; Rhonda Bassel-Duby; Eric N Olson

doi:10.1073/pnas.1411251111

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Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription factor

Journal article

Open access

Peer reviewed

Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription factor

Chengzu Long, Chad E Grueter, Kunhua Song, Song Qin, Xiaoxia Qi, Y Megan Kong, John M Shelton, James A Richardson, Chun-Li Zhang, Rhonda Bassel-Duby, …

Proceedings of the National Academy of Sciences - PNAS, Vol.111(31), pp.11521-11526

08/05/2014

DOI: 10.1073/pnas.1411251111

PMCID: PMC4128133

PMID: 25049392

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Abstract

Members of the calmodulin-binding transcription activator (CAMTA) family of proteins function as calcium-sensitive regulators of gene expression in multicellular organisms ranging from plants to humans. Here, we show that global or nervous system deletion of CAMTA1 in mice causes severe ataxia with Purkinje cell degeneration and cerebellar atrophy, partially resembling the consequences of haploinsufficiency of the human CAMTA1 locus. Gene-expression analysis identified a large collection of neuronal genes that were dysregulated in the brains of CAMTA1-mutant mice, and elucidation of a consensus sequence for binding of CAMTA proteins to DNA revealed the association of CAMTA-binding sites with many of these genes. We conclude that CAMTA1 plays an essential role in the control of Purkinje cell function and survival. CAMTA1-mutant mice provide a model to study the molecular mechanisms of neurodegenerative diseases and for screening potential therapeutic interventions for such disorders.

Nucleotide Motifs - genetics

Protein Multimerization

Transcription Factors - deficiency

Molecular Sequence Data

Male

Motor Activity

Base Sequence

Integrases - metabolism

Ataxia - metabolism

Binding Sites

Ataxia - pathology

Calcium-Binding Proteins - metabolism

Inverted Repeat Sequences - genetics

Ataxia - physiopathology

Purkinje Cells - metabolism

Gene Expression Regulation

Calcium-Binding Proteins - deficiency

AT Rich Sequence

Mice, Knockout

Nestin - metabolism

Transcription Factors - metabolism

Animals

Trans-Activators - deficiency

Trans-Activators - metabolism

Mice

Purkinje Cells - pathology

Details

Title: Subtitle: Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription factor
Creators: Chengzu Long - Departments of Molecular Biology
Chad E Grueter - Departments of Molecular Biology
Kunhua Song - Departments of Molecular Biology
Song Qin - Departments of Molecular Biology
Xiaoxia Qi - Departments of Molecular Biology
Y Megan Kong - Departments of Molecular Biology
John M Shelton - Internal Medicine, and
James A Richardson - Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390
Chun-Li Zhang - Departments of Molecular Biology
Rhonda Bassel-Duby - Departments of Molecular Biology
Eric N Olson - Departments of Molecular Biology
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.111(31), pp.11521-11526
DOI: 10.1073/pnas.1411251111
PMID: 25049392
PMCID: PMC4128133
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 08/05/2014
Academic Unit: Cardiovascular Medicine; Craniofacial Anomalies Research Center; Internal Medicine
Record Identifier: 9984094547302771

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