The alpha-chemokine CXCL14 is up-regulated in the sciatic nerve of a mouse model of Charcot-Marie-Tooth disease type 1A and alters myelin gene expression in cultured Schwann cells.
At present the pathogenesis of CMT1A neuropathy, caused by the overexpression of PMP22, has not yet been entirely understood. The PMP22-overexpressing C61 mutant mouse is a suitable animal model, which mimics the human CMT1A disorder. We observed that myelin gene expression in the sciatic nerve of the C61 mouse was up-regulated at postnatal day 4 to 7 (P4-P7). When investigating the morphology of peripheral nerves in C61 and wildtype mice at early stages of postnatal development, hypermyelination could be detected in the femoral quadriceps and sciatic nerve of transgenic animals at postnatal day 7 (P7). In order to identify genes, other than Pmp22, that are modulated in sciatic nerve of P7 transgenic mice, we applied microarray technology. Amongst the regulated genes, the gene encoding the alpha-chemokine CXCL14 was most prominently up-regulated. We report that Cxcl14 was expressed exclusively by Schwann cells of the sciatic nerve, as well as by cultured Schwann cells triggered to differentiate. Furthermore, in cultured Schwann cells CXCL14 modulated the expression of myelin genes and altered cell proliferation. Our findings demonstrate that early overexpression of PMP22, in a mouse model of CMT1A, results in a strong up-regulation of CXCL14, which seems to play a novel regulatory role in Schwann cell differentiation.
Barbaria
Elena M
EM
Molecular Neurobiology Laboratory, Department of Neurology, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
Kohl
Bianca
B
Buhren
Bettina A
BA
Hasenpusch-Theil
Kerstin
K
Kruse
Fabian
F
Küry
Patrick
P
Martini
Rudolf
R
Müller
Hans Werner
HW
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000378:metabolism; D019743:Chemokines, CXC / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000235:genetics* / Q000378:metabolism; D018993:Myelin P0 Protein / Q000235:genetics* / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000378:metabolism*; D015854:Up-Regulation
C517518:CXCL14 protein, mouse; D019743:Chemokines, CXC; D004676:Myelin Basic Protein; D018993:Myelin P0 Protein; D009185:Myelin Proteins; C073687:PMP22 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins