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M. Klein, C. C. Jung, R. R. McInnes, D. G. Birch; Absence of Transcription Factor Prdm8 Leads to Stationary Night Blindness in Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4188.
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© ARVO (1962-2015); The Authors (2016-present)
Congenital stationary night blindness (CSNB) is a retinal disorder with disturbed night vision. In traditional models of CSNB, like the nob mice (Pardue et al, IOVS 1998; 39), the loss of function is caused by a defect in synaptic transmission between photoreceptors and rod-bipolar cells (Gregg, IOVS 2003; 44), leading to an electronegative electroretinogram (ERG). In contrast, mice without PR-domain containing 8 (Prdm8) exhibit a complete absence of rod-bipolar cells and fewer cone bipolar cells (C. Jung et al, ARVO abstract, 2007). To determine the consequences of the absence of rod-bipolar function, we performed ERG testing on Prdm8 -/- mice.
Three 3-month-old Prdm8 -/- mice were compared to 3 age-matched Prdm8 +/- and 3 WT littermates. ERGs were conducted following the ISCEV standard protocol adapted for mice. A-waves were elicited with high-intensity flashes (1.12 - 631 cd/m2). Light-adapted cone responses were elicited on a rod-saturating background.
Knockout mice showed significantly diminished rod b-waves (70.8 µV) in response to moderate stimuli (0.4 cd/m2) when compared to WT mice (143.5 µV). Prdm8 +/- mice did not differ significantly from WT mice (p=0.65).The standard combined response was reduced (p=0.008) without showing negative polarity. The high-intensity a-wave Rmp3 in Prdm8 -/- mice showed a 12.4 % reduction (p=0.005). The cone b-wave was also significantly diminished (p=0.02). The a/b amplitude ratio in knockout mice was 1:3 versus 1:4 in WT mice (p=0.004).
Absence of Prdm8 leads to diminished rod ERGs showing a more severely affected b-wave than a-wave. The reduction of cone signals in Prdm8 knockout mice may be due to loss of Type 2 OFF cone bipolar cells. Abnormal synaptic connections between rod photoreceptors and cone-bipolars, resulting in competition between rods and cones may also play a role. The Prdm8 model differs from previous mouse models and may be a useful tool in studying human forms of CSNB.
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