C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/12 (2006.01) A01K 67/027 (2006.01) C07K 14/47 (2006.01) C12N 5/10 (2006.01) C12N 15/85 (2006.01) C12N 15/89 (2006.01) C12N 15/90 (2006.01) C12Q 1/00 (2006.01) G01N 33/48 (2006.01)
Patent
CA 2150092
Proteolipid protein and its isoprotein DM20, the two splice products of the PLP gene, are the two major membrane proteins of CNS myelin. For structural and functional analysis during myelination we replaced the PLP gene in mouse ES- cells by a mutated PLP targeting construct (deletion of 105 bp at the 3' end of exon III) with an antisense (as) oriented neo-gene in intron III, (plp- /dm20+/asneo). Brain RNAs of transgenic mice unexpectedly are devoid of PLP and DM20 mRNAs, PLP and DM20 isoproteins are completely missing in myelin. The plasma membrane processes of oligodendrocytes of the PLP-deficient mouse are spirally wrapped around axons of large diameter but have lost their compacted structure, smaller axons are non- or hypomyelinated. Young transgenic mice manifest no severe loss of CNS functions, although the conductance velocity is reduced by one half in PLP-deficient mice. These results define PLP as an essential membrane component responsible for the highly ordered myelin sheath ofCNS axons.
Boison Detlev
Stoffel Wilhelm
Aktiengesellschaft Bayer
Fetherstonhaugh & Co.
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