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Table 3 Proteolipid protein (PLP) mutant mouse models show glial activation

From: Clinically relevant intronic splicing enhancer mutation in myelin proteolipid protein leads to progressive microglia and astrocyte activation in white and gray matter regions of the brain

Mouse model Type of mutation PMD Major pathology Reactive glia response
PLP1-null [26] Targeted KO of PLP and DM20 yes [48, 49] Myelin ↔ / OL # ↔ / motor ↓↓↓ @ 16mo / normal lifespan Astrocytes ↑↑ / microglia ↑↑ after 12 months [22]
PLP-ISEdel [35] KI of intronic splicing enhancer yes [34] Myelin ↔ / OL # ↔ / motor ↓ / normal lifespan Astrocytes ↑↑↑ / microglia ↑↑↑ [current]
PLP1dub [21] Genomic duplication PLP1 locus yes [50] Myelin ↓ / OL # (nr) / motor ↓↓ / lifespan (nr) Astrocytes ↑↑ / microglia ↑↑ [21]
PLP1tg [20] Overexpresses native PLP1   Myelin ↓↓ / OL # ↓↓ / motor ↓↓↓/ lethal (2 to 6 months) Astrocytes ↑↑↑ / microglia ↑↑↑ [16, 19, 20]
PLP1-rsh [51] Spontaneous single amino acid substitution yes [52] Myelin ↓↓ / OL # ↔ / motor ↓↓ / normal lifespan Astrocytes ↑↑ / microglia ↑↑ [18]
PLP1-jp [53] Spontaneous deletion of exon 5   Myelin ↓↓↓ / OL # ↓↓↓ / motor ↓↓↓ / lethal (around P30) Astrocytes ↑↑ / microglia ↑↑ [16, 17]
PLP1-msd [54] Spontaneous mutation of exon 6 yes [55] Myelin ↓↓↓/ OL # ↓↓↓ / motor ↓↓ / lethal (around P30) Astrocytes ↑↑↑ / microglia ↑↑↑ [15]
  1. PLP mutant mice models are sorted by the severity of the pathophysiology, and summarized for type of PLP mutation, if mutation is found in clinical PMD population, major pathology (myelin/oligodendrocyte death/motor behavior ability/premature mortality) and reactive glia (astrocyte and microglia). Abbreviations: oligodendrocyte (OL); arrows indicate degree of change = no change ↔, mild ↑ or ↓, moderate ↑↑ or ↓↓, severe ↑↑↑ or ↓↓↓, or not reported (nr). Numbers in brackets represent relevant references.