Early defect in the expression of mouse sperm DnaJ 1, a member of the DNAJ/heat shock protein 40 chaperone protein family, in the spinal cord of the wobbler mouse, a murine model of motoneuronal degeneration

• Published in: Neuroscience Vol. 113; no. 4; pp. 825 - 835
• Main Authors: Boillée, S, Berruti, G, Meccariello, R, Grannec, G, Razan, F, Pierantoni, R, Fasano, S, Junier, M.P
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2002; Elsevier
• Subjects: Animals; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Down-Regulation - physiology; heat shock proteins; Heat-Shock Proteins - biosynthesis; Heat-Shock Proteins - genetics; HSP40 Heat-Shock Proteins; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred NZB; Mice, Neurologic Mutants; motoneuron; Motor Neuron Disease - genetics; Motor Neuron Disease - metabolism; Msj-1; Mutation - physiology; neurodegeneration; Neurology; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Spermatozoa - metabolism; Spinal Cord - metabolism; Testis - metabolism; EGTA, ethylene glycol-bis(2-aminoethylether)- N, N, N′, N′-tetraacetic acid; SOD1, superoxide dismutase 1 enzyme; neurodegeneration; SDS, sodium dodecyl sulfate; HEPES, N-(2-hydroxyethyl)piperazine- N′-(2-ethanesulfonic acid); ALS, amyotrophic lateral sclerosis; HSP, heat shock proteins; PBS, phosphate-buffered saline; motoneuron; ANOVA, analysis of variance; EDTA, ethylene diaminetetra-acetate; Msj-1; heat shock proteins; Msj-1, mouse sperm DnaJ 1; RT-PCR, reverse transcription-polymerase chain reaction; Animal model; Nervous system diseases; Spinal cord; Spermatozoa; Rodentia; Central nervous system; Motor neuron; Gene expression; Vertebrata; Mammalia; Mouse; Heat shock protein; Degeneration; Acrosome
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(02)00235-X

Prevention of protein misfolding is ensured by chaperone proteins, including the heat shock proteins (HSP) of the DNAJ/HSP40 family. Detection of abnormal protein aggregates in various neurodegenerative diseases has led to the proposal that altered chaperone activity contributes to neurodegeneration. Msj-1, a DNAJ/HSP40 protein located around the spermatozoa acrosome, was recently found to be down-regulated in the testis of wobbler mutant mice. Wobbler is an unidentified recessive mutation which triggers progressive motoneuron degeneration with abnormal intracellular protein accumulations, and defective spermatozoa maturation. Here, we examined Msj-1 expression in the spinal cord of the mutants and their controls. Msj-1 transcripts were amplified by reverse transcription-polymerase chain reaction from mutant and wild-type spinal cord RNA. Sequencing of Msj-1 coding region revealed no change in the mutant. In contrast, decreased Msj-1 mRNA levels were observed in five to six-week-old wobbler mice spinal cord, when motoneuron degeneration is at its apex, as compared to controls. A similar decrease was observed in two-week-old wobbler spinal cord, when the number of motoneurons is still unaltered, indicating that the decreased mRNA content is intrinsic to the mutant and not simply related to the loss of cells expressing Msj-1. Assays of Msj-1 protein levels yielded similar results. Immunofluorescent labeling revealed numerous Msj-1-ir motoneurons in five-week-old control spinal cord while no signal was observed in age-matched wobbler. Our results show, therefore, that Msj-1 expression is down-regulated in both organs affected by the wobbler mutation, the CNS and the testis, and that this defect precedes the first histological signs of motoneuron degeneration. These results provide the first example of an association between transcriptional repression of a chaperone protein and a neurodegenerative process.