Purchase this article with an account.
M.E. Pennesi, D. Bramblett, M.–J. Tsai, S.M. Wu; ERGs from Bhlhb4 knockout mice reveal normal rod–driven a–waves but severely diminished b–waves . Invest. Ophthalmol. Vis. Sci. 2004;45(13):789.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Loss of the basic helix loop helix (Bhlh) transcription factor, BETA2/NeuroD1, has been implicated in retinal degeneration in animal models. We now investigate the role of a related transcription factor, Bhlhb4, in retinal function. Methods: Bhlhb4 knockout mice (Bhlhb4KO) with the LacZ gene knocked into the Bhlhb4 coding region were generated to determine the in vivo function of Bhlhb4. To test retinal function, full field electroretinograms (ERGs) were measured from wild–type, heterozygous null, and homozygous null mutant mice at 1–3 months. Changes in retinal structure were examined using both light and confocal microscopy. Results: Staining for LacZ activity revealed that Bhlhb4–LacZ expression in the retina is restricted to the inner nuclear layer. Comparison of retinal marker genes to Bhlhb4–LacZ by immunofluorescent labeling suggested that Bhlhb4 is expressed in a subset of bipolar cells. ERGs recorded from wild–type and mutant mice revealed no significant difference in the rod–driven a–wave, suggesting that phototransduction was intact. However, the rod driven b–wave, a measure of bipolar cell activity, was dramatically reduced, resulting in a negative waveform of the ERG. This phenotype is commonly associated with certain forms of congenital stationary night blindness (CSNB). Conclusions: The lack of Bhlhb4 results in a severe loss of retinal bipolar cell function. We are now conducting molecular biological, histological and electrophysiological experiments to decipher the mechanism of Bhlhb4 action and to determine if mice lacking Bhlhb4 may be a new model for autosomal recessive CSNB.
This PDF is available to Subscribers Only