ZFP191 is required by oligodendrocytes for CNS myelination.
The controlling factors that prompt mature oligodendrocytes to myelinate axons are largely undetermined. In this study, we used a forward genetics approach to identify a mutant mouse strain characterized by the absence of CNS myelin despite the presence of abundant numbers of late-stage, process-extending oligodendrocytes. Through linkage mapping and complementation testing, we identified the mutation as a single nucleotide insertion in the gene encoding zinc finger protein 191 (Zfp191), which is a widely expressed, nuclear-localized protein that belongs to a family whose members contain both DNA-binding zinc finger domains and protein-protein-interacting SCAN domains. Zfp191 mutants express an array of myelin-related genes at significantly reduced levels, and our in vitro and in vivo data indicate that mutant ZFP191 acts in a cell-autonomous fashion to disrupt oligodendrocyte function. Therefore, this study demonstrates that ZFP191 is required for the myelinating function of differentiated oligodendrocytes.
Howng
Shen Yi B
SY
Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA;
Avila
Robin L
RL
Emery
Ben
B
Traka
Maria
M
Lin
Wensheng
W
Watkins
Trent
T
Cook
Susan
S
Bronson
Roderick
R
Davisson
Muriel
M
Barres
Ben A
BA
Popko
Brian
B
D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000196:embryology; D004622:Embryo, Mammalian / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*
D002352:Carrier Proteins; C474810:Zfp24 protein, mouse