Browsing by Author "Chen, Ching-Kang"

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    Modulation of CREB in the Dorsal Lateral Geniculate Nucleus of Dark-Reared Mice
    Krahe, Thomas E.; Seabrook, Tania A.; Chen, Ching-Kang; Fox, Michael A.; Guido, William (Hindawi, 2012)
    The cAMP-response element-binding protein (CREB) plays an important role in visual cortical plasticity that follows the disruption of sensory activity, as induced by dark rearing (DR). Recent findings indicate that the dorsal lateral geniculate nucleus (dLGN) of thalamus is also sensitive to altered sensory activity. DR disrupts retinogeniculate synaptic strength and pruning in mice, but only when DR starts one week after eye opening (delayed DR, DDR) and not after chronic DR (CDR) from birth.While DR upregulates CREB in visual cortex, whether it also modulates this pathway in dLGN remains unknown. Here we investigate the role of CREB in the dLGN of mice that were CDR or DDR using western blot and immunofluorescence. Similar to findings in visual cortex, CREB is upregulated in dLGN after CDR and DDR. These findings are consistent with the proposal that DR up-regulates the CREB pathway in response to decreased visual drive.
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    Non-Cell Autonomous Roles for CASK in Optic Nerve Hypoplasia
    Kerr, Alicia; Patel, Paras A.; LaConte, Leslie E. W.; Liang, Chen; Chen, Ching-Kang; Shah, Veeral; Fox, Michael A.; Mukherjee, Konark (ARVO, 2019)
    PURPOSE. Heterozygous mutations in the essential X-linked gene CASK associate with optic nerve hypoplasia (ONH) and other retinal disorders in girls. CASKþ/ heterozygous knockout mice with mosaic CASK expression exhibit ONH with a loss of retinal ganglion cells (RGCs) but no changes in retinal morphology. It remains unclear if CASK deficiency selectively affects RGCs or also affects other retinal cells. Furthermore, it is not known if CASK expression in RGCs is critical for optic nerve (ON) development and maintenance. METHODS. The visual behavior of CASKþ/ mice was assessed and electroretinography (ERG) was performed. Using a mouse line with a floxed CASK gene that expresses approximately 40% CASK globally in all cells (hypomorph) under hemizygous and homozygous conditions, we investigated effects of CASK reduction on the retina and ON. CASK then was completely deleted from RGCs to examine its cell-autonomous role. Finally, for the first time to our knowledge, we describe a hemizygous CASK missense mutation in a boy with ONH. RESULTS. CASKþ/ heterozygous mutant mice display reduced visual contrast sensitivity, but ERG is indistinguishable from wildtype. CASK hypomorph mice exhibit ONH, but deletion of CASK from RGCs in this background does not exacerbate the condition. The boy with ONH harbors a missense mutation (p.Pro673Leu) that destabilizes CASK and weakens the crucial CASK–neurexin interaction. CONCLUSIONS. Our results demonstrate that mosaic or global reduction in CASK expression and/or function disproportionately affects RGCs. CASK expression in RGCs does not appear critical for cell survival, indicating a noncell autonomous role for CASK in the development of ON.