NACS Seminar: Dr. Zubair Ahmed
Calcium and Integrin binding protein 2 (CIB2) is essential for hearing and vision
Usher syndrome (USH) is a neurosensory disorder defined by a bilateral sensorineural deafness and a loss of vision due to retinitis pigmentosa (RP), with a prevalence estimate of 1/6000 individuals in the US. Genetic and functional studies of the protein determinants of USH have been fruitful in elucidating the common molecular components and shared signaling networks in the inner ear and retinal sensory epithelia. We previously identified the CIB2 gene as the cause of Usher syndrome type 1 (USH1J) and non-syndromic deafness (DFNB48) in 61 human families. CIB2, as member of calcium- and integrin-binding proteins, changes conformation upon Ca2+ binding. In the inner ear, CIB2 is localized at the upper ends of the hair cells’ stereocilia, near the tip link-mechanoelectrical transduction complex. CIB2 is also expressed in the retinal pigmented epithelium besides other retinal sensory cells. We used mouse models to elucidate the molecular and cellular auditory and retinal pathophysiology associated with loss of CIB2 function. Our results revealed the necessity of CIB2 for the functional sound and light transduction in humans and mice. A major barrier to developing treatments for USH1 has been a lack of relevant murine models that faithfully mimic the characteristic human RP phenotype. Comparison with the human USH phenotype confirm the utility and validity of our animal models.
Usher syndrome (USH) is a neurosensory disorder defined by a bilateral sensorineural deafness and a loss of vision due to retinitis pigmentosa (RP), with a prevalence estimate of 1/6000 individuals in the US. Genetic and functional studies of the protein determinants of USH have been fruitful in elucidating the common molecular components and shared signaling networks in the inner ear and retinal sensory epithelia. We previously identified the CIB2 gene as the cause of Usher syndrome type 1 (USH1J) and non-syndromic deafness (DFNB48) in 61 human families. CIB2, as member of calcium- and integrin-binding proteins, changes conformation upon Ca2+ binding. In the inner ear, CIB2 is localized at the upper ends of the hair cells’ stereocilia, near the tip link-mechanoelectrical transduction complex. CIB2 is also expressed in the retinal pigmented epithelium besides other retinal sensory cells. We used mouse models to elucidate the molecular and cellular auditory and retinal pathophysiology associated with loss of CIB2 function. Our results revealed the necessity of CIB2 for the functional sound and light transduction in humans and mice. A major barrier to developing treatments for USH1 has been a lack of relevant murine models that faithfully mimic the characteristic human RP phenotype. Comparison with the human USH phenotype confirm the utility and validity of our animal models.
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