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.
Saleh
Maria-Carla
MC
Unité d'Expression des Gènes Eucaryotes, Institut Pasteur, Paris, France.
Espinosa de los Monteros
Araceli
A
de Arriba Zerpa
Gonzalo A
GA
Fontaine
Isabelle
I
Piaud
Oriane
O
Djordjijevic
Dragan
D
Baroukh
Nadine
N
Garcia Otin
Angel Luis
AL
Ortiz
Esteban
E
Lewis
Sandra
S
Fiette
Laurence
L
Santambrogio
Paolo
P
Belzung
Catherine
C
Connor
James R
JR
de Vellis
Jean
J
Pasquini
Juana M
JM
Zakin
Mario M
MM
Baron
Bruno
B
Guillou
Florian
F
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