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Transgenic complementation of rumpshaker with wild type proteolipid protein

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  • Qh301 Biology
  • Sf600 Veterinary Medicine
  • Biology
  • Medicine


Mutations in the x-linked myelin proteolipid protein 1 gene (PLP1) cause the heterogeneous syndromes of Pelizaeus Merzbacher disease (PMD) and Spastic paraplegia type 2(SPG2) in man (Hudson et al., 2004). A single base change mutation in our spontaneous mouse model rumpshaker (Plpjp-rsh)(Ile186Thr) (Schneider et al., 1992) generates a misfolded protein resulting in dysmyelination and increased numbers of apoptotic oligodendrocytes. The phenotype varies from mild on the original C3H background to lethal when backcrossed onto the C57BL/6 mouse strain (Al-Saktawi et al., 2003). Utilising the more severe variant we sought to ameliorate the lethal phenotype by transgenic complementation with wild type Plp1 (Readhead et al., 1994) to normalise the levels of proteolipid protein (PLP) and it’s smaller isoform DM20. The presence of the wild type protein improves the survival of the mice, decreases oligodendrocyte apoptosis and restores normal periodicity to the myelin, however hypomyelination remains severe. Although the PLP/DM20 level is restored to normal the level of myelin basic protein remains low. In addition the presence of the wild type protein does not ameliorate the unfolded protein response induced by the rumpshaker PLP/DM20.

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