title: Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription factor.
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.
authors: Departments of Molecular Biology.
authors: Chengzu
authors: C
authors: Long
authors: Departments of Molecular Biology.
authors: Chad E
authors: CE
authors: Grueter
authors: Departments of Molecular Biology.
authors: Kunhua
authors: K
authors: Song
authors: Departments of Molecular Biology.
authors: Song
authors: S
authors: Qin
authors: Departments of Molecular Biology.
authors: Xiaoxia
authors: X
authors: Qi
authors: Departments of Molecular Biology.
authors: Y Megan
authors: YM
authors: Kong
authors: Internal Medicine, and.
authors: John M
authors: JM
authors: Shelton
authors: Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors: James A
authors: JA
authors: Richardson
authors: Departments of Molecular Biology.
authors: Chun-Li
authors: CL
authors: Zhang
authors: Departments of Molecular Biology.
authors: Rhonda
authors: R
authors: Bassel-Duby
authors: Departments of Molecular Biology.
authors: Eric N
authors: EN
authors: Olson
mesh_terms: D020856:AT Rich Sequence; D000818:Animals; D001259:Ataxia / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D001483:Base Sequence; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000172:deficiency* / Q000378:metabolism; D005786:Gene Expression Regulation; D019426:Integrases / Q000378:metabolism; D055029:Inverted Repeat Sequences / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009043:Motor Activity; D064231:Nestin / Q000378:metabolism; D059372:Nucleotide Motifs / Q000235:genetics; D055503:Protein Multimerization; D011689:Purkinje Cells / Q000378:metabolism* / Q000473:pathology*; D015534:Trans-Activators / Q000172:deficiency* / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency* / Q000378:metabolism
chemical_list: C000591996:CAMTA1 protein, mouse; D002135:Calcium-Binding Proteins; D064231:Nestin; D015534:Trans-Activators; D014157:Transcription Factors; C045073:Cre recombinase; D019426:Integrases
keywords: CAMTA2; dimerization; neural genes; palindromic DNA