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J.M. Harrison, S. Gu, J.X. Jiang; Electroretinogram (ERG) and Flash Visual Evoked Potential (fVEP) of the Glutamine Transporter, Mouse N–System Amino Acid Transporter (mNAT2) Knockout Mouse . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3761.
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mNAT2 has been characterized and localized predominantly in the ganglion cells and their axons and in the brain of the mouse (J. Biol Chem 276:24137–44, 2001). The specificity of mNAT2 for promoting glutamine transport has been determined; and, finally, mice with a knockout (KO) of the gene encoding mNAT2 have been generated. The purpose of the study was to characterize the function of the visual system of the mNAT2 KO mouse by ERG and fVEP.
Full–field ERGs and fVEPs were produced by flashes with 8 luminances from 0.0003 to 7 cd sc s m–2 in 3 mNAT2 KO and 2 WT mice. ERGs (1–1000 Hz) were recorded from the apical cornea of the left eye. The fVEPs were recorded with a subdermal active electrode under the occipital scalp. The reference electrode for both was a subdermal electrode in the lower jaw. Low (1–55 Hz) and high (55–200 Hz) band–pass filtered ERG were extracted by a finite impulse response filter. The b–wave amplitudes were derived from the low band–pass filtered ERGs. The integral of the rectified high band–pass ERGs between from 0–0.1 s after the flash was the measure of oscillatory potentials (OPs). ERG data were compared to those of 10 WT C57Bl/6 mice. The amplitude and implicit time of the major negative component of the fVEP were measured.
Mean a– and b–wave and integrated OP amplitudes of the ERGs produced by the maximum luminance in the mNAT2 KO mice were greater than those of the WT: –465 and 888 microvolts, and 39 microvolt s vs. –228 and 737, 22; but all amplitudes fell within 2 standard deviations of the mean of the amplitudes of the ERGs produced by the same stimulus in 10 C57Bl/6 mice. The mean amplitude and implicit time of the fVEP produced by the maximum luminance in the mNAT2 KO mice were slightly greater than those produced in the WT mice –57 microvolts, 0.052 s vs. –45 microvolts 0.048 s.
Glutamine is the principal precursor for glutamate, the major neurotransmitter of the ganglion cells. The current data, at this stage in these mice, exclude the possibility of a major retinal degeneration or a significant depletion of ganglion cell glutamate because of the presence of robust ERG components from the outer, middle, and inner retina and large fVEPs with normal implicit times in the mNAT2 KO mice. We are continuing to collect data to produce a sample size sufficient to detect or exclude smaller differences and to investigate recovery time after bleaching flashes. Absence of the mNAT2 may slow repletion of glutamate after a significant depletion and thus slow recovery time after a bright flash.
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