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Ko Park, Grace Randazzo, Tatiana Eliseeva, Kenneth L. Jones, Joseph A Brzezinski; Tmem215 and Trnp1 are novel bipolar-specific genes in the mouse retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2243.
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© ARVO (1962-2015); The Authors (2016-present)
The mechanisms that regulate bipolar cell genesis are incompletely understood. Mice that lack the transcription factor Prdm1 precociously form bipolar cells at the expense of photoreceptors. To discover early bipolar cell factors, we identified the genes that were upregulated in Prdm1 mutant retinas.
Postnatal day (P) 2 retinas from five Prdm1 conditional null mice and five controls were processed for high throughput RNA-sequencing. Genes that were statistically different between conditions and that increased at least 40% were considered candidate bipolar-specific factors. Candidates were further evaluated by in situ hybridization and immunohistochemistry. For one gene, Tmem215, LacZ knock-in mice were constructed to better trace gene expression in the retina.
RNA-seq comparison between P2 Prdm1 conditional null and control retinas revealed about 80 significantly upregulated genes. We further characterized the expression of two genes that have unknown function in the retina, Tmem215 (a transmembrane protein) and Trnp1 (TMF-regulated nuclear protein). Both genes were expressed in the postnatal retina by in situ hybridization and remained expressed in the inner nuclear layer of the adult retina. Using antibodies to Trnp1 and other subtype markers, we observed that Trnp1 expression was limited to ON type bipolar cells. To trace Tmem215, we used Tmem215LacZ heterozygous knock-in mice. b-galactosidase expression was restricted to about 40% of bipolar cells.
We have identified two novel bipolar-specific genes by searching for precociously upregulated genes in Prdm1 mutant retinas. The expression of both Tmem215 and Trnp1 closely paralleled the spatial and temporal pattern of bipolar cell genesis. In the future, we will test whether Tmem215 and Trnp1 regulate bipolar cell specification and maturation.
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