title: C9ORF72 expression and cellular localization over mouse development.
abstract: BACKGROUND
  A majority of familial frontotemporal lobar dementia and amyotrophic lateral sclerosis cases are associated with a large repeat expansion in a non-coding region of the C9ORF72 gene. Currently, little is known about the normal function and the expression pattern of the C9ORF72 protein. The aims of this study were to characterize the expression pattern and cellular localization of the three reported mouse isoforms of C9orf72, over a developmental time-course in primary cultured cortical neurons and brain tissue from C57BL/6 mice.
  
  
  RESULTS
  We demonstrated that the different isoforms of C9ORF72 at the mRNA and protein level undergo alterations in expression during development and into adulthood. Cellular fractionation and immunofluorescence demonstrated that levels of nuclear and cytoplasmic expression of isoforms changed significantly over the time course. Additionally, immunofluorescence studies showed C9ORF72 labeling as puncta throughout neurons, extending beyond the microtubule cytoskeleton into actin-rich structures such as filopodia and growth cones. Finally, synaptosome preparations demonstrated the presence of C9ORF72 isoform 1 in synaptic-rich fractions from adult mouse brain.
  
  
  CONCLUSIONS
  In summary, the presence of C9ORF72 as puncta and within synaptic-rich fractions may indicate involvement at the synapse and differential expression of isoforms in nuclei and cytoplasm may suggest distinct roles for the isoforms. Determining the physiological role of C9ORF72 protein may help to determine the role it plays in disease.
authors.affiliation: Wicking Dementia Research and Education Centre, Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Rachel A K
authors.initials: RA
authors.lastname: Atkinson
authors.affiliation: Wicking Dementia Research and Education Centre, Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Fernandez-Martos
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, North Ryde, New South Wales, Australia.
authors.forename: Julie D
authors.initials: JD
authors.lastname: Atkin
authors.affiliation: Wicking Dementia Research and Education Centre, Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: James C
authors.initials: JC
authors.lastname: Vickers
authors.affiliation: Wicking Dementia Research and Education Centre, Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia. A.E.King@utas.edu.au.
authors.forename: Anna E
authors.initials: AE
authors.lastname: King
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000073885:C9orf72 Protein; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology* / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019579:Neocortex / Q000166:cytology* / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D000073885:C9orf72 Protein; C000606498:C9orf72 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2