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Characterization of Gap Junction Proteins in the Bladder of Cx43 Mutant Mouse Models of Oculodentodigital Dysplasia

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Abstract

Oculodentodigital dysplasia (ODDD) is a rare developmental disease resulting from germline mutations in the GJA1 gene that encodes the gap junction protein connexin43 (Cx43). In addition to the classical ODDD symptoms that affect the eyes, teeth, bone and digits, in some cases ODDD patients have reported bladder impairments. Thus, we chose to characterize the bladder in mutant mouse models of ODDD that harbor two distinct Cx43 mutations, G60S and I130T. Histological assessment revealed no difference in bladder detrusor wall thickness in mutant compared to littermate control mice. The overall localization of Cx43 in the lamina propria and detrusor also appeared to be similar in the bladders of mutant mice with the exception that the G60S mice had more instances of intracellular Cx43. However, both mutant mouse lines exhibited a significant reduction in the phosphorylated P1 and P2 isoforms of Cx43, while only the I130T mice exhibited a reduction in total Cx43 levels. Interestingly, Cx26 levels and distribution were not altered in mutant mice as it was localized to intracellular compartments and restricted to the basal cell layers of the urothelium. Our studies suggest that these two distinct genetically modified mouse models of ODDD probably mimic patients who lack bladder defects or other factors, such as aging or co-morbidities, are necessary to reveal a bladder phenotype.

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Acknowledgments

The authors thank Kevin Barr for breeding and maintaining the genetically modified mice used in the current study. D.W.L. was funded by the Canadian Institutes of Health Research and the Canada Research Chair Program.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Western University, London, ON, Canada

    R. Lorentz, Q. Shao, T. Huang & D. W. Laird

  2. Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY, USA

    G. I. Fishman

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  1. R. Lorentz
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  2. Q. Shao
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  3. T. Huang
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  4. G. I. Fishman
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  5. D. W. Laird
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Correspondence to D. W. Laird.

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Lorentz, R., Shao, Q., Huang, T. et al. Characterization of Gap Junction Proteins in the Bladder of Cx43 Mutant Mouse Models of Oculodentodigital Dysplasia. J Membrane Biol 245, 345–355 (2012). https://doi.org/10.1007/s00232-012-9455-1

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  • DOI: https://doi.org/10.1007/s00232-012-9455-1

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