Loss of locus coeruleus neurons and reduced startle in parkin null mice

Rainer Von Coelln, Bobby Thomas, Joseph M. Savitt, Kah Leong Lim, Masayuki Sasaki, Ellen J. Hess, Valina L. Dawson, Ted M. Dawson

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247 Citations (Scopus)

Abstract

Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized pathologically by degeneration of catecholaminergic neurons of the substantia nigra pars compacta and locus coeruleus, among other regions. Autosomal-recessive juvenile Parkinsonism (ARJP) is caused by mutations in the PARK2 gene coding for parkin and constitutes the most common familial form of PD. The majority of ARJP-associated parkin mutations are thought to be loss of function-mutations; however, the pathogenesis of ARJP remains poorly understood. Here, we report the generation of parkin null mice by targeted deletion of parkin exon 7. These mice show a loss of catecholaminergic neurons in the locus coeruleus and an accompanying loss of norepinephrine in discrete regions of the central nervous system. Moreover, there is a dramatic reduction of the norepinephrine-dependent startle response. The nigrostriatal dopaminergic system does not show any impairment. This mouse model will help gain a better understanding of parkin function and the mechanisms underlying parkin-associated PD.

Original languageEnglish (US)
Pages (from-to)10744-10749
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number29
DOIs
StatePublished - Jul 20 2004

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Locus Coeruleus
Parkinsonian Disorders
Parkinson Disease
Neurons
Mutation
Norepinephrine
Startle Reflex
Nerve Degeneration
Movement Disorders
Neurodegenerative Diseases
Exons
Central Nervous System
Genes

ASJC Scopus subject areas

  • General

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Von Coelln, R., Thomas, B., Savitt, J. M., Lim, K. L., Sasaki, M., Hess, E. J., ... Dawson, T. M. (2004). Loss of locus coeruleus neurons and reduced startle in parkin null mice. Proceedings of the National Academy of Sciences of the United States of America, 101(29), 10744-10749. https://doi.org/10.1073/pnas.0401297101

Loss of locus coeruleus neurons and reduced startle in parkin null mice. / Von Coelln, Rainer; Thomas, Bobby; Savitt, Joseph M.; Lim, Kah Leong; Sasaki, Masayuki; Hess, Ellen J.; Dawson, Valina L.; Dawson, Ted M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 29, 20.07.2004, p. 10744-10749.

Research output: Contribution to journalArticle

Von Coelln, R, Thomas, B, Savitt, JM, Lim, KL, Sasaki, M, Hess, EJ, Dawson, VL & Dawson, TM 2004, 'Loss of locus coeruleus neurons and reduced startle in parkin null mice', Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 29, pp. 10744-10749. https://doi.org/10.1073/pnas.0401297101
Von Coelln, Rainer ; Thomas, Bobby ; Savitt, Joseph M. ; Lim, Kah Leong ; Sasaki, Masayuki ; Hess, Ellen J. ; Dawson, Valina L. ; Dawson, Ted M. / Loss of locus coeruleus neurons and reduced startle in parkin null mice. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 29. pp. 10744-10749.
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