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Rupalatha Maddala, Vann G Bennett, Vasanth Rao; Conditional Deficiency of Ankyrin-B Impairs Lens Growth and Transparency in Mice. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1711.
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Ankyrin-B (AnkB), a well characterized adaptor protein which tethers the spectrin-actin cytoskeleton to membrane proteins and plays a role in membrane subdomain organization, has been reported to influence lens fiber cell cytoarchitecture. Understanding of the definitive role of AnkB in lens function however, has remained elusive. In this study we have therefore developed and characterized an AnkB conditional knockout mouse in order to determine the role of this protein in lens function and integrity.
AnkB lens conditional knockout (cKO) mice were generated using AnkB floxed and lens Cre transgenic mice (Le-Cre). Eyes derived from neonatal and postnatal AnkB cKO mice and from littermate Le-Cre control mice were evaluated for histological, biochemical and morphological changes.
Consistent with the observations recorded in AnkB null mice, neonatal (P1) AnkB cKO mice do not show any noticeable changes either in lens morphogenesis or integrity. Postnatal AnkB cKO mice (after P16) however, rapidly develop cataracts with a significant decrease in eye and lens weight relative to AnkB floxed or Le-Cre control mice. Postnatal AnkB cKO mice (P19 & P21) exhibit intense nuclear cataract together with gross degeneration, swelling and membrane disruption of lens fibers. The recorded lens phenotype in the AnkB cKO mice was confirmed to be associated with deficiency of AnkB by immunoblot analyses. Studies are in progress to determine the cellular and molecular basis for the AnkB deficiency induced decrease in lens size and cataract formation using P7 and P16 AnkB cKO mice.
This ongoing study demonstrates a requirement for AnkB in lens growth, architecture and transparency and suggests a vital role for the scaffolding activity of AnkB in fiber cell adhesive interactions, cytoarchitecture and membrane organization.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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