P0-Cre transgenic mice for inactivation of adhesion molecules in Schwann cells.
Normal peripheral nerve myelination depends on Schwann cell-basal lamina interactions. An important component of Schwann cell basal lamina is laminin--predominantly laminins 2 and 4. Mutations in the alpha 2 chain common to these two isoforms are associated with dysmyelination in mouse (dy) and man (congenital muscular dystrophy). Thus, laminin 2 and 4 receptors are also likely to be important for myelin formation. Several laminin 2/4 receptors are detected at the basal lamina surface of myelin-forming Schwann cells, namely, alpha 6 beta 4 and alpha 6 beta 1 integrins and dystroglycan. The evidence linking these receptors to myelination is suggestive, but not conclusive. Genetic studies have not yet confirmed a role for these molecules in myelin formation. Natural or targeted inactivation of alpha 6, beta 4, and beta 1 integrins and of dystroglycan have profound effects on other tissues causing embryonic or perinatal death before myelination. Therefore, to conditionally inactivate these receptors specifically in myelin-forming Schwann cells, we have constructed and initially characterized a P0-Cre transgene that activates Cre-mediated recombination of loxP-containing genes in peripheral nerve.
Feltri
M L
ML
Department of Neurology, San Raffaele Scientific Institute, Milano, Italy. 1.feltri@hsr.it
D'Antonio
M
M
Previtali
S
S
Fasolini
M
M
Messing
A
A
Wrabetz
L
L
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018993:Myelin P0 Protein / Q000235:genetics / Q000502:physiology*; D009928:Organ Specificity; D017474:Receptors, Laminin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000502:physiology*; D012584:Sciatic Nerve / Q000502:physiology / Q000648:ultrastructure; D014764:Viral Proteins; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D007797:Laminin; D018993:Myelin P0 Protein; D017474:Receptors, Laminin; D011994:Recombinant Proteins; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases; D001616:beta-Galactosidase