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Expression of a Myelin Proteolipid Protein (Plp)-lacZ Transgene is Reduced in both the CNS and PNS of Plp jp Mice

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Abstract

Jimpy (Plp jp) is an X-linked recessive mutation in mice that causes CNS dysmyelination and early death in affected males. It results from a point mutation in the acceptor splice site of myelin proteolipid protein (Plp) exon 5, producing transcripts that are missing exon 5, with a concomitant shift in the downstream reading frame. Expression of the mutant PLP product in Plp jp males leads to hypomyelination and oligodendrocyte death. Expression of our Plp-lacZ fusion gene, PLP(+)Z, in transgenic mice is an excellent readout for endogenous Plp transcriptional activity. The current studies assess expression of the PLP(+)Z transgene in the Plp jp background. These studies demonstrate that expression of the transgene is decreased in both the central and peripheral nervous systems of affected Plp jp males. Thus, expression of mutated PLP protein downregulates Plp gene activity both in oligodendrocytes, which eventually die, and in Schwann cells, which are apparently unaffected in Plp jp mice.

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Acknowledgments

This work was supported by a grant from the National Institutes of Health (NS25304, WBM) and a postdoctoral fellowship from the National Multiple Sclerosis Society (CSD). The authors thank Dannette DeWeese, Leigh Hayes and Tom Phan for technical assistance.

Author information

Author notes

  1. Cynthia S. Duchala

    Present address: Centocor, Inc., 145 King of Prussia Road, Radnor, PA, 19087, USA

  2. Tatyana I. Gudz

    Present address: Department of Neurosciences, Medical University of South Carolina, 114 Doughty St., Rm 338, Charleston, SC, 29425, USA

Authors and Affiliations

  1. Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA

    Patricia A. Wight

  2. Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA

    Cynthia S. Duchala, H. Elizabeth Shick, Tatyana I. Gudz & Wendy B. Macklin

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  1. Patricia A. Wight
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  2. Cynthia S. Duchala
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Corresponding author

Correspondence to Wendy B. Macklin.

Additional information

Special issue dedicated to Anthony Campagnoni.

Patricia A. Wight and Cynthia S. Duchala contributed equally to this study.

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Wight, P.A., Duchala, C.S., Shick, H.E. et al. Expression of a Myelin Proteolipid Protein (Plp)-lacZ Transgene is Reduced in both the CNS and PNS of Plp jp Mice. Neurochem Res 32, 343–351 (2007). https://doi.org/10.1007/s11064-006-9202-z

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  • DOI: https://doi.org/10.1007/s11064-006-9202-z

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