A5009314461- Hearing, Cochlea, Tinnitus, Genetics
- RNA and protein synthesis mechanisms
- Hearing Loss and Rehabilitation
- Vestibular and auditory disorders
- Biochemical Analysis and Sensing Techniques
- Ion channel regulation and function
- Ion Channels and Receptors
- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Cancer-related molecular mechanisms research
- Virus-based gene therapy research
- Congenital heart defects research
- RNA Research and Splicing
- Animal Genetics and Reproduction
- RNA regulation and disease
- CRISPR and Genetic Engineering
- Autism Spectrum Disorder Research
- Muscle Physiology and Disorders
- Mitochondrial Function and Pathology
- interferon and immune responses
- Monoclonal and Polyclonal Antibodies Research
- Effects of Environmental Stressors on Livestock
- Cleft Lip and Palate Research
- Spine and Intervertebral Disc Pathology
University of Michigan
2011-2022
Kresge Eye Institute
2022
Michigan United
2018
University of Nottingham
1997
InDex Pharmaceuticals (Sweden)
1996
Upon trauma, the adult murine peripheral nervous system (PNS) displays a remarkable degree of spontaneous anatomical and functional regeneration. To explore extrinsic mechanisms neural repair, we carried out single-cell analysis naïve mouse sciatic nerve, blood mononuclear cells, crushed nerves at 1 day, 3 days, 7 days following injury. During first week, monocytes macrophages (Mo/Mac) rapidly accumulate in injured nerve undergo extensive metabolic reprogramming. Proinflammatory Mo/Mac with...
Analysis of a transgene-induced mutation at the mouse med locus led to identification novel voltage-gated sodium channel gene Scn8a (Burgess, D. L., Kohrman, C., Galt, J., Plummer, N. W., Jones, J. M., Spear, B., and Meisler, M. H.(1995) Nat. Genet. 10, 461-465). We now report splicing defects in two spontaneous mutations Scn8a. The original was caused by insertion truncated LINE element into exon 2 transcript is spliced from 1 cryptic acceptor site intron 2. A 4-base pair deletion within 5'...
The voltage-gated sodium channel Scn8a is broadly distributed in brain and spinal cord. We have identified a missense mutation that associated with cerebellar ataxia the jolting mutant, mild allele of "motor endplate disease" locus. results substitution Thr for an evolutionarily conserved Ala residue cytoplasmic S4-S5 linker domain III. Introduction corresponding into rat IIA shifted voltage dependence activation by 14 mV depolarizing direction, without affecting kinetics fast inactivation...
Noise exposures causing only transient threshold shifts can destroy auditory-nerve synapses without damaging hair cells. Here, we asked whether virally mediated neurotrophin3 (NT3) overexpression repair this damage. CBA/CaJ mice at 6 wks were injected unilaterally with adeno-associated virus (AAV) containing either NT3 or GFP genes, via the posterior semicircular canal, 3 prior to, 5 hrs after, noise exposure. Controls included exposed animals receiving vehicle only, and unexposed virus....
More than 360 million humans are affected with some degree of hearing loss, either early or later in life. A genetic cause for the disorder is present a majority cases. We mapped locus (DFNB101) loss to chromosome 5q consanguineous Pakistani family. Exome sequencing revealed an insertion mutation GRXCR2 as moderate-to-severe and likely progressive individuals The frameshift predicted affect conserved, cysteine-rich region GRXCR2, result abnormal extension C-terminus. Functional studies by...
Abstract Age‐related hearing loss (ARHL) is the most prevalent sensory deficit in elderly. This progressive pathology often has psychological and medical comorbidities, including social isolation, depression, cognitive decline. Despite ARHL's enormous societal economic impact, no therapies to prevent or slow its progression exist. Loss of synapses between inner hair cells (IHCs) spiral ganglion neurons (SGNs), a.k.a. IHC synaptopathy, an early event cochlear aging, preceding neuronal cell...
Stable interactions between simian virus 40 large T antigen and host proteins are believed to play a major role in the ability of viral protein transform cells culture induce tumors vivo. Two these proteins, retinoblastoma susceptibility (pRB) p53, products tumor suppressor genes, suggesting that exerts at least portion its transforming activity by complexing with inactivating function proteins. While analyzing antigen-host complexes mouse cells, we noted 185 kDa (p185) which specifically...
SLC44A2 (solute carrier 44a2), also known as CTL2 (choline transporter-like protein 2), is expressed in many supporting cell types the cochlea and implicated hair survival antibody-induced hearing loss. In mice with mixed C57BL/6-129 background, homozygous deletion of Slc44a2 exons 3–10 (Slc44a2 Δ/Δ) resulted high-frequency loss death. To reduce effects associated age-related (ARHL) these strains, carrying Δ allele were backcrossed to ARHL-resistant FVB/NJ strain evaluated after backcross...
The inner ear is a complex organ containing sensory tissue, including hair cells, the development of which not well understood. Our long-term goal to discover genes critical for correct formation and function its tissue. A novel gene, transmembrane (Tmie), was found cause hearing-related disorders when defective in mice humans. homologous tmie gene zebrafish cloned expression characterized between 24 51 hours post-fertilization. Embryos injected with morpholinos (MO) directed against...
Our previous study demonstrated rapamycin added to diet at 4 months of age had significantly less age-related outer hair cell loss in the basal half cochlea 22 compared mice without rapamycin. The present tested adding later life, 14 age, and a longitudinal assessment auditory brain stem response (ABR). used UMHET4 mice, way cross which all grandparental strains lack Cdh23 753A allele that predisposes early onset, progressive hearing loss. typically have normal until 16–17 months, then...
Hearing and balance depend upon the precise morphogenesis mechanosensory function of stereocilia, specialized structures on apical surface sensory hair cells in inner ear. Previous studies Grxcr1 mutant mice indicated a critical role for this gene control stereocilia dimensions during development. In study, we analyzed expression paralog Grxcr2 mouse evaluated auditory vestibular strains carrying targeted mutations gene. Peak occurs early postnatal development ear GRXCR2 is localized to both...
Abstract A dominant mutation was generated in transgenic mice as a consequence of insertional mutation. Heterozygous from line 9257 (Tg9257) are hyperactive with bidirectional circling behavior and have distinctive facial appearance due to hypoplasia the nasal bone. Morphological analysis inner ear revealed asymmetric abnormalities horizontal canal flattening or invagination crista ampullaris, which can account for behavior. The sensory epithelium appeared be normal. transgene insertion site...