The long term goals of this project are to define the functions of tight junctions in Stria vascularis of the inner ear and to determine if the diversity of Claudin family members that comprise fight junctions located around Scala media have overlapping or non-overlapping properties. The knowledge gained from these studies will provide deep insights into the roles of the stria vascularis in hearing and potassium recycling to the endolymph.
The specific aims are: 1) to test the hypothesis that inner ear pathology in Claudin//-null mice stems from morphological defects. Claudin 11 is expressed in the developing vestibulocochlear apparatus of embryos from E13.5 as well as in adults and evidence of gross structural changes during development and postnatally that could account for the pathology in the knockout mice will be sought. 2) to test the hypothesis that Claudin 11-null mice exhibit early hearing defects. Young adult knockout mice exhibit elevated auditory brainstem response (ABR) thresholds which indicate hearing loss, Further testing of ABRs as well as measurements of endocochlear potentials and DPOAEs at different ages will reveal if this phenotype is progressive or present at the time mice normally start to hear. 3) to optimize a transgene cassette for the expression of heterologous genes in basal cells of Stria vascularis. Basal cell-specific enhancer elements already in-hand will be located within the Claudin 11 gene and used to drive expression of a beta-galactosidase reporter gene in the cochlea, Reporter expression will be characterized with a view to expressing several claudin cDNAs in the cochlea in attempts to rescue hearing loss in Claudin 11-null mice.
| Maheras, Kathleen J; Peppi, Marcello; Ghoddoussi, Farhad et al. (2018) Absence of Claudin 11 in CNS Myelin Perturbs Behavior and Neurotransmitter Levels in Mice. Sci Rep 8:3798 |
| Maheras, Kathleen June; Pindolia, Kirit; Wolf, Barry et al. (2017) Developmental window of sensorineural deafness in biotinidase-deficient mice. J Inherit Metab Dis 40:733-744 |
| Denninger, Andrew R; Breglio, Andrew; Maheras, Kathleen J et al. (2015) Claudin-11 Tight Junctions in Myelin Are a Barrier to Diffusion and Lack Strong Adhesive Properties. Biophys J 109:1387-97 |
| Maheras, Kathleen J; Gow, Alexander (2013) Increased anesthesia time using 2,2,2-tribromoethanol-chloral hydrate with low impact on mouse psychoacoustics. J Neurosci Methods 219:61-9 |
| Southwood, Cherie M; Lipovich, Leonard; Gow, Alexander (2012) Tissue-restricted transcription from a conserved intragenic CpG island in the Klf1 gene in mice. Biol Reprod 87:108 |
| Wu, Xin; Peppi, Marcello; Vengalil, Matthew J et al. (2012) Transgene-mediated rescue of spermatogenesis in Cldn11-null mice. Biol Reprod 86:139, 1-11 |
| Mazaud-Guittot, Severine; Gow, Alexander; Le Magueresse-Battistoni, Brigitte (2011) Phenotyping the claudin 11 deficiency in testis: from histology to immunohistochemistry. Methods Mol Biol 763:223-36 |
| Devaux, Jérôme; Fykkolodziej, Bozena; Gow, Alexander (2010) Claudin Proteins And Neuronal Function. Curr Top Membr 65:229-253 |
| Mazaud-Guittot, S; Meugnier, E; Pesenti, S et al. (2010) Claudin 11 deficiency in mice results in loss of the Sertoli cell epithelial phenotype in the testis. Biol Reprod 82:202-13 |
| Gow, Alexander; Devaux, Jerome (2008) A model of tight junction function in central nervous system myelinated axons. Neuron Glia Biol 4:307-17 |
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