Oligodendrocyte differentiation is increased in transferrin transgenic mice.
Transferrin (Tf), the iron transport glycoprotein found in biological fluids of vertebrates, is synthesized mainly by hepatocytes. Tf is also synthesized by oligodendrocytes (Ol), and several lines of evidence indicate that brain Tf could be involved in myelinogenesis. Because Tf is postnatally expressed in the brain, we sought to investigate whether Tf could intervene in Ol differentiation. For this purpose, we analyzed transgenic mice overexpressing the complete human Tf gene in Ol. We show that the hTf transgene was expressed only from 5 days postpartum onward. In the brain of 14-day-old transgenic mice, the DM-20 mRNA level was decreased, whereas the PLP, MBP, CNP, and MAG mRNA levels were increased. We counted a higher proportion of Ol expressing the O4 (Ol-specific antigens) and PLP in brain cells cultured from transgenic mice. These results support the idea that overexpressing Tf in the brain accelerates the oligodendrocyte lineage maturation. Accordingly, by NMR imaging acquisition of diffusion tensor in hTf transgenic mice, we observed early maturation of the cerebellum and spinal cord and more myelination in the corpus callosum. In addition, hTf overexpression led to an increase in Sox10 mRNA and protein. Increases in Sox10 and in Tf expression occur simultaneously during brain development. The Olig1 mRNA level also increased, but long after the rise of hTf and Sox10. The Olig2 mRNA level remained unchanged in the brain of transgenic mice. Our findings suggest that Tf could influence oligodendrocyte progenitor differentiation in the CNS.
Sow
Amina
A
Unité Physiologie de la Reproduction et des Comportements (PRC), Institut National de la Recherche Agronomique, UMR 6175 INRA-CNRS-Université de Tours-Haras Nationaux, Nouzilly, France.
Lamant
Matthieu
M
Bonny
Jean-Marie
JM
Larvaron
Pierre
P
Piaud
Oriane
O
Lécureuil
Charlotte
C
Fontaine
Isabelle
I
Saleh
Maria-Carla
MC
Garcia Otin
Angel Luis
AL
Renou
Jean-Pierre
JP
Baron
Bruno
B
Zakin
Mario
M
Guillou
Florian
F
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000235:genetics / Q000378:metabolism; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D001835:Body Weight / Q000235:genetics; D001921:Brain / Q000166:cytology; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000502:physiology*; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology; D012333:RNA, Messenger / Q000302:isolation & purification; D011863:Radioimmunoassay / Q000379:methods; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D014168:Transferrin / Q000235:genetics* / Q000378:metabolism
C104739:Mag protein, mouse; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D009419:Nerve Tissue Proteins; C047516:Plp1 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D014168:Transferrin; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases