title: Changes in TDP-43 expression in development, aging, and in the neurofilament light protein knockout mouse.
abstract: The transactive response DNA-binding protein 43 (TDP-43) has been identified as a neurofilament light (NF-L) messenger RNA (mRNA)-binding protein. Abnormally increased levels of TDP-43 are detected in patients with amyotrophic lateral sclerosis and a downregulation of NF-L mRNA. However, links between NF-L and TDP-43 expressions are unclear. In this study, we investigated whether the deficiency of NF-L protein can result in alterations in TDP-43 localization or protein expression and whether this is altered with aging. There was a significant increase in TDP-43 protein levels in the cortex and lumbar spinal cord in 12-month-old NF-L knockout (NF-L KO) mice, compared with wild-type (WT) C57BL/6 mice. However, there was no difference in either the phosphorylation of TDP-43 between WT and NF-L KO mice or the abnormal mislocalization of TDP-43 to the cytoplasm in NF-L KO animals. Our findings suggest that NF-L protein or mRNA may negatively affect the expression of TDP-43 in the central nervous system. However, altered phosphorylation of TDP-43 may be more highly associated with aging than the levels of TDP-43 expression.
authors.affiliation: Wicking Dementia Research and Education Centre, Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
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: Wicking Dementia Research and Education Centre, Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Matthew T K
authors.initials: MT
authors.lastname: Kirkcaldie
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Biomedical Center, Uppsala, Sweden.
authors.forename: Hao
authors.initials: H
authors.lastname: Cui
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. Electronic address: A.E.King@utas.edu.au.
authors.forename: Anna E
authors.initials: AE
authors.lastname: King
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D055786:Gene Knockout Techniques; D006801:Humans; D008297:Male; D018345:Mice, Knockout; D016900:Neurofilament Proteins / Q000172:deficiency / Q000235:genetics*; D010766:Phosphorylation; D012333:RNA, Messenger; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D016900:Neurofilament Proteins; D012333:RNA, Messenger; C578077:Tardbp protein, mouse; C044882:neurofilament protein L
keywords: Amyotrophic lateral sclerosis (ALS); Neurofilament light (NF-L); Phosphorylated TDP-43; Transactive response DNA-binding protein 43 (TDP-43)