Reference : Quantitative trait locus mapping identifies a locus linked to striatal dopamine and p...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/48896
Quantitative trait locus mapping identifies a locus linked to striatal dopamine and points to collagen IV alpha-6 chain as a novel regulator of striatal axonal branching in mice
English
Thomas, Melanie mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology >]
Gui, Yujuan [Department of Life Sciences and Medicine (DLSM), University of Luxembourg, Belvaux, Luxembourg]
Garcia, Pierre mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology >]
Karout, Mona [Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch/Alzette, Luxembourg]
Gomez Ramos, Borja mailto [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
Jaeger, Christian [Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch/Alzette, Luxembourg]
Michelucci, Alessandro [Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch/Alzette, Luxembourg > > > ; Neuro-Immunology Group, Department of Oncology (DONC), Luxembourg Institute of Health (LIH), Luxembourg, Luxembourg]
Gaigneaux, Anthoula mailto [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
Kollmus, Heike [Department of Infection Genetics, Helmholtz Centre for Infection Research, Braunschweig, Germany]
Centeno, Arthur [Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee, USA]
Schughart, Klaus [Department of Infection Genetics, Helmholtz Centre for Infection Research, Braunschweig, Germany > > > ; University of Veterinary Medicine Hannover, Hannover, Germany > > > ; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, USA]
Balling, Rudi [Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch/Alzette, Luxembourg]
Mittelbronn, Michel [Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch/Alzette, Luxembourg > > > ; Luxembourg Centre of Neuropathology (LCNP), Luxembourg > > > ; National Center of Pathology (NCP), Laboratoire National de Santé (LNS), Dudelange, Luxembourg]
Nadeau, Joseph H. [Pacific Northwest Research Institute, Seattle, Washington, USA > > > ; Maine Medical Center Research Institute, Scarborough, Maine, USA]
Sauter, Thomas mailto [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
Williams, Robert W. [Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee, USA]
Sinkkonen, Lasse mailto [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
Buttini, Manuel mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology >]
9-Aug-2021
Genes, Brain, and Behavior
Blackwell
Yes (verified by ORBilu)
International
1601-1848
1601-183X
Oxford
United Kingdom
[en] collaborative cross ; dopamine ; nigrostriatal circuit
[en] Dopaminergic neurons (DA neurons) are controlled by multiple factors, many involved in neurological disease. Parkinson's disease motor symptoms are caused by the demise of nigral DA neurons, leading to loss of striatal dopamine (DA). Here, we measured DA concentration in the dorsal striatum of 32 members of Collaborative Cross (CC) family and their eight founder strains. Striatal DA varied greatly in founders, and differences were highly heritable in the inbred CC progeny. We identified a locus, containing 164 genes, linked to DA concentration in the dorsal striatum on chromosome X. We used RNAseq profiling of the ventral midbrain of two founders with substantial difference in striatal DA–C56BL/6 J and A/J—to highlight potential protein-coding candidates modulating this trait. Among the five differentially expressed genes within the locus, we found that the gene coding for the collagen IV alpha 6 chain (Col4a6) was expressed nine times less in A/J than in C57BL/6J. Using single cell RNA-seq data from developing human midbrain, we found that COL4A6 is highly expressed in radial glia-like cells and neuronal progenitors, indicating a role in neuronal development. Collagen IV alpha-6 chain (COL4A6) controls axogenesis in simple model organisms. Consistent with these findings, A/J mice had less striatal axonal branching than C57BL/6J mice. We tentatively conclude that DA concentration and axonal branching in dorsal striatum are modulated by COL4A6, possibly during development. Our study shows that genetic mapping based on an easily measured Central Nervous System (CNS) trait, using the CC population, combined with follow-up observations, can parse heritability of such a trait, and nominate novel functions for commonly expressed proteins.
Fonds National de la Recherche - FnR, Helmholtz-Association
Researchers
http://hdl.handle.net/10993/48896
10.1111/gbb.12769
FnR ; FNR10406131 > Manuel Buttini > DANeuroGEN > Identifying Novel Genetic And Epigenetic Modulators Of Dopaminergic Neuron Structure And Function. > 01/05/2016 > 30/04/2019 > 2015

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