This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Burgess, R. W. Articles by O'Brien, T. P. Search for Related Content PubMed PubMed Citation Articles by Burgess, R. W. Articles by O'Brien, T. P.

Evidence for a Conserved Function in Synapse Formation Reveals Phr1 as a Candidate Gene for Respiratory Failure in Newborn Mice

The Jackson Laboratory, Bar Harbor, Maine 04609

Received 8 May 2003/ Returned for modification 16 September 2003/ Accepted 28 October 2003

Genetic studies using a set of overlapping deletions centered at the piebald locus on distal mouse chromosome 14 have defined a genomic region associated with respiratory distress and lethality at birth. We have isolated and characterized the candidate gene Phr1 that is located within the respiratory distress critical genomic interval. Phr1 is the ortholog of the human Protein Associated with Myc as well as Drosophila highwire and Caenorhabditis elegans regulator of presynaptic morphology 1. Phr1 is expressed in the embryonic and postnatal nervous system. In mice lacking Phr1, the phrenic nerve failed to completely innervate the diaphragm. In addition, nerve terminal morphology was severely disrupted, comparable with the synaptic defects seen in the Drosophila hiw and C. elegans rpm-1 mutants. Although intercostal muscles were completely innervated, they also showed dysmorphic nerve terminals. In addition, sensory neuron terminals in the diaphragm were abnormal. The neuromuscular junctions showed excessive sprouting of nerve terminals, consistent with inadequate presynaptic stimulation of the muscle. On the basis of the abnormal neuronal morphology seen in mice, Drosophila, and C. elegans, we propose that Phr1 plays a conserved role in synaptic development and is a candidate gene for respiratory distress and ventilatory disorders that arise from defective neuronal control of breathing.

This article has been cited by other articles:

• Li, H., Kulkarni, G., Wadsworth, W. G. (2008). RPM-1, a Caenorhabditis elegans Protein That Functions in Presynaptic Differentiation, Negatively Regulates Axon Outgrowth by Controlling SAX-3/robo and UNC-5/UNC5 Activity. J. Neurosci. 28: 3595-3603 [Abstract] [Full Text]  
• Bloom, A. J., Miller, B. R., Sanes, J. R., DiAntonio, A. (2007). The requirement for Phr1 in CNS axon tract formation reveals the corticostriatal boundary as a choice point for cortical axons. Genes Dev. 21: 2593-2606 [Abstract] [Full Text]  
• Yi, J. J., Ehlers, M. D. (2007). Emerging Roles for Ubiquitin and Protein Degradation in Neuronal Function. Pharmacol. Rev. 59: 14-39 [Abstract] [Full Text]  
• Burgess, R. W., Jucius, T. J., Ackerman, S. L. (2006). Motor Axon Guidance of the Mammalian Trochlear and Phrenic Nerves: Dependence on the Netrin Receptor Unc5c and Modifier Loci. J. Neurosci. 26: 5756-5766 [Abstract] [Full Text]  
• Wu, C., Wairkar, Y. P., Collins, C. A., DiAntonio, A. (2005). Highwire Function at the Drosophila Neuromuscular Junction: Spatial, Structural, and Temporal Requirements. J. Neurosci. 25: 9557-9566 [Abstract] [Full Text]  
• D'Souza, J., Hendricks, M., Le Guyader, S., Subburaju, S., Grunewald, B., Scholich, K., Jesuthasan, S. (2005). Formation of the retinotectal projection requires Esrom, an ortholog of PAM (protein associated with Myc). Development 132: 247-256 [Abstract] [Full Text]