His36Pro point-mutated proteolipid protein retained in the endoplasmic reticulum of oligodendrocytes in the Shaking pup

✍ Scribed by Jonathan Song; Brian D. Goetz; Ian D. Duncan

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 547 KB
• Volume: 53
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/glia.20279

✦ Synopsis

Abstract

The shaking pup (shp) is a canine mutation that affects the myelin protein proteolipid protein (PLP) and its smaller and less abundant isoform, DM20, with proline replacing histidine^36^, resulting in a severe myelin deficiency in the central nervous system. We present evidence that the mutation leads to disrupted trafficking of the shp PLP/DM20 within oligodendrocytes. Immunohistochemical studies revealed significantly reduced levels of PLP/DM20 and other major myelin components such as myelin basic protein (MBP), myelin associated glycoprotein (MAG), and 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase (CNP) in shp myelin. The distribution of shp PLP/DM20 proteins were altered and mostly retained in perinuclear cytoplasm and proximal processes, which co‐localized with distended rough endoplasmic reticulum (RER) within oligodendrocytes. No abnormal accumulation of MAG, MBP, or CNP in the cell body was found. These results suggest that mutated PLP/DM20 in the shp could be selectively retained in RER, causing disruption of their translocation to the periphery to myelinate axons. © 2005 Wiley‐Liss, Inc.