Myelination and motor coordination are increased in transferrin transgenic mice

Maria Carla Saleh, Araceli Espinosa De los Monteros, Gonzalo A. De Arriba Zerpa, Isabelle Fontaine, Oriane Piaud, Dragan Djordjijevic, Nadine Baroukh, Angel Luis Garcia Otin, Esteban Ortiz, Sandra Lewis, Laurence Fiette, Paolo Santambrogio, Catherine Belzung, James R. Connor, Jean De Vellis, Juana M. Pasquini, Mario M. Zakin, Bruno Baron, Florian Guillou

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)587-594
Number of pages8
JournalJournal of Neuroscience Research
Volume72
Issue number5
DOIs
Publication statusPublished - Jun 1 2003

Keywords

  • Central nervous system
  • Myelin deficiency
  • Transferrin

ASJC Scopus subject areas

  • Neuroscience(all)

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