A Transgenic Mouse Model for Human Hereditary Neuropathy with Liability to Pressure Palsies

• Published in: Molecular and cellular neuroscience Vol. 8; no. 6; pp. 405 - 416
• Main Authors: Maycox, Peter R., Ortuño, Daniel, Burrola, Patrick, Kuhn, Rainer, Bieri, Phyllis L., Arrezo, Joseph C., Lemke, Greg
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 1997
• Subjects: Animals; Antisense Elements (Genetics); Behavior, Animal - physiology; Female; Genetic Predisposition to Disease; Humans; Mice; Mice, Transgenic - genetics; Myelin Proteins - genetics; Neural Conduction; Paralysis - genetics; Peripheral Nervous System Diseases - genetics; Peripheral Nervous System Diseases - physiopathology; Peripheral Nervous System Diseases - psychology; Phenotype; Pressure; RNA, Messenger - metabolism; Sciatic Nerve - pathology
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1006/mcne.1997.0600

Mutations in the gene encoding peripheral myelin protein 22 (PMP22) account for several inherited peripheral neuropathies in humans. We now show that transgenic mice expressing antisense PMP22 RNA exhibit modestly reduced levels of PMP22 together with a phenotype that is reminiscent of hereditary neuropathy with liability to pressure palsies (HNPP), a human disease caused by a 1.5-Mb deletion of a chromosome 17 region that contains thePMP22gene. Transgenic antisense homozygotes display a striking movement disorder and a slowing of nerve conduction that worsens with age. Morphological analysis of peripheral nerves demonstrates that a subset of axons have thickened myelin sheaths and tomacula in young adults, with significant myelin degeneration detected in older animals. Together with other recent work, these data suggest that dosage of thePMP22gene alone underlies the pathophysiology observed in HNPP and related disorders.