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D.S. Rice, J.J. Schrick, P. Vogel, A.T. Sands, B.P. Zambrowicz; Mice Lacking ADP–ribosylation Factor–like 3 (Arl3) Exhibit Retinal Degeneration and Polycystic Kidney Disease . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5236.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: ADP–ribosylation–like factors (known as ARLs) belong to the RAS superfamily of GTP–binding proteins. Mutations in Arl6 have recently been identified in Bardet–Biedl syndrome type 3, which is characterized by blindness and systemic abnormalities in humans. Another ARL family member, Arl3, is known to interact with the retinitis pigmentosa 2 (RP2) protein and the delta subunit of rod–specific cyclic GMP phosphodiesterase, suggesting an important role for Arl3 in photoreceptor biology. Mice lacking Arl3 were used to study the function of this protein. Methods: Mice deficient in Arl3 were generated from Omnibank, a sequence–tagged gene–trap library of >270,000 mouse embryonic stem cell clones. Routine diagnostics, histopathology, electron microscopy, and immunohistochemistry were used to characterize mice lacking Arl3. Results: Breedings between heterozygous Arl3 mice produced fewer Arl3 homozygous mice than expected, indicating reduced viability in mice lacking Arl3. Histological analysis of retinas obtained from 2 week old mice revealed photoreceptor degeneration. High levels of rhodopsin immunoreactivity were detected in photoreceptor cell bodies in mice lacking Arl3, whereas strong immunoreactivity was localized in outer segments in wild type mice. PNA staining revealed abnormal cone morphology in mice deficient in Arl3. Furthermore, disruption of Arl3 resulted in abnormal development of renal, hepatic, and pancreatic epithelial tubule structures, characteristic of the renal–hepatic–pancreatic dysplasia found in autosomal recessive polycystic kidney disease. Conclusions: Mice deficient in Arl3 fail to thrive and exhibit retinal and systemic abnormalities that are consistent with a role for ARLs in cytoskeleton functions and intracellular trafficking.
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