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J.D. Ochrietor, K.S. Alligood, T. Muramatsu, P.J. Linser; Impaired Lactate Transport in 5A11/Basigin Null Mouse Retina Neurons . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1714.
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Purpose: 5A11/Basigin null mice have dysfunctional photoreceptor cells. The ERG response of these animals is severely depressed from the time of eye opening. It has been demonstrated that 5A11/Basigin gene products interact with monocarboxylate transporter 1 (MCT1). We propose that a lactate shuttle composed of 5A11/Basigin gene products and MCT1 is necessary for photoreceptor cell function. We hypothesize that the absence of this lactate shuttle in the 5A11/Basigin null mouse underlies the retinal dysfunction observed in these animals. We therefore sought to determine whether photoreceptor cells from 5A11/Basigin null mice transport lactate. Methods: Neuronal cells from 5A11/Basigin null mice and control littermates were cultured and loaded with the cell–permeant AM ester acetate of seminaphthorhodafluor (SNARF), a pH–sensitive dye. The cells were excited at 488 nm and the emission at both 580 nm and 640 nm was monitored before and after the addition of 5 mM, 10 mM, and 20 mM lactate. The ratios of the 580 nm: 640 nm emissions before and after lactate incubation were compared to determine the pH change in the cells. Results: The normal neurons became acidic after addition of the lactate, when compared to untreated controls. The 580 nm: 640 nm ratio increased after the addition of lactate. The neurons from 5A11/Basigin null mice did not become acidic after the addition of lactate. The 580 nm: 640 nm ratio decreased in the null cells. Conclusions: These data suggest that neurons from normal mice can actively transport lactate, whereas the neurons from 5A11/Basigin null mice cannot. The null cells do not express either 5A11/Basigin gene product and do not have MCT1 at the plasma membrane. The results of our studies support our hypothesis that a lactate shuttle deficiency underlies the retinal dysfunction of the 5A11/Basigin null mouse since the null neurons cannot transport lactate.
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