Myelination and motor coordination are increased in transferrin transgenic mice.
Myelin deficiency in the central nervous system (CNS) can cause severe disabling conditions. Most of the transgenic mice models overexpressing myelin components have limitations for investigators of myelin deficiency and myelin therapy as they severely alter CNS architecture. It has been postulated that transferrin (Tf) is involved in oligodendrocyte (OL) maturation and myelinogenesis. Because Tf is not an intrinsic myelin constituent, we decided to investigate if its overexpression could have an impact on the myelination process without affecting myelin integrity. We generated transgenic mice containing the complete human Tf gene specifically overexpressed in OLs. This overexpression leads to more than a 30% increase in myelin components, such as galactolipids, phospholipids, and proteins. Electron microscopy showed that myelin is structurally normal in terms of thickness and compaction. Behavior analysis showed that mice do not display significant modifications in their locomotion and cognitive and emotional abilities. Furthermore, in one of the genetic background, animals presented a significant increase in motor coordination. We did not find any modification in OL number during early postnatal development, suggesting that Tf does not act on OL proliferation. In addition, the levels of iron and ferritin remained unchanged in the brain of transgenic mice compared to control mice. Our findings indicate that, besides its known iron transport function, Tf is able to influence myelination process and induce behavioral improvements in mice.
Unité d'Expression des Gènes Eucaryotes, Institut Pasteur, Paris, France.
Maria-Carla
MC
Saleh
Araceli
A
Espinosa de los Monteros
Gonzalo A
GA
de Arriba Zerpa
Isabelle
I
Fontaine
Oriane
O
Piaud
Dragan
D
Djordjijevic
Nadine
N
Baroukh
Angel Luis
AL
Garcia Otin
Esteban
E
Ortiz
Sandra
S
Lewis
Laurence
L
Fiette
Paolo
P
Santambrogio
Catherine
C
Belzung
James R
JR
Connor
Jean
J
de Vellis
Juana M
JM
Pasquini
Mario M
MM
Zakin
Bruno
B
Baron
Florian
F
Guillou
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002490:Central Nervous System / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D020233:Gait Disorders, Neurologic / Q000235:genetics; D038983:Galactolipids / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009068:Movement / Q000502:physiology*; D009185:Myelin Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D014168:Transferrin / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*
D038983:Galactolipids; D009185:Myelin Proteins; D010743:Phospholipids; D014168:Transferrin