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Dee Schramm, Peter Fuerst; Aberrant axon development and up-regulation of c-Jun is associated with eye opening in Down’s syndrome cell adhesion molecule mutant. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5159.
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© ARVO (1962-2015); The Authors (2016-present)
Down’s syndrome cell adhesion molecule (DSCAM) is thought to mediate cell repulsion and possibly apoptosis during retinal development in the mouse. A mutant strain of mice in our laboratory (Dscam2j), null for DSCAM, exhibits disorganized retinal lamination, aberrant synaptic organization, and markedly greater numbers of ganglion cells in the retina compared to wild type counterparts on postnatal day 15. The objectives of this study were to 1) characterize the axon phenotype before and after eye opening in Dscam2j compared to wild type mice, 2) characterize ganglion cell number and size before and after eye opening in Dscam2j compared to wild type mice, and 3) characterize expression of c-jun, phosphorylated c-jun, and GFAP before and after eye opening in Dscam2j compared to wild type mice.
Immunohistochemistry, western blot analysis, and RT-PCR were used to characterize phenotypic differences in retinas from Dscam2j and wild type mice before and at various time points after eye opening and into adulthood.
Aberrant axon phenotypes were observed after eye opening in Dscam2j compared to wild type mice. Mutant mice exhibited ganglion cell hypertrophy and hyperplasia before eye opening compared to wild type mice. Both c-jun and phosphorylated c-jun were markedly up regulated in ganglion cells after eye opening in Dscam2j compared to wild type mice. Phosphorylated c-jun was the predominant form of c-jun observed after eye opening.
DSCAM may play an essential role in retinal development in conjunction with the onset of vision. The up regulation of c-jun, and particularly phosphorylated c-jun, may likely be indicative of a stress response that may or may not play a role in the aberrant phenotypes observed. Results of the present study may extend our understanding of c-jun in retinal development and ultimately lead to a better understanding of the molecular basis of how DSCAM is involved in retinal neurogenesis.
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