GNAT1, encoding the rod-specific transducin α-subunit, is a key element in the rod phototransduction cascade in the retina [1,2]. Phototransduction is a crucial pathway for converting light into neural signals, thus GNAT1 is of great biological importance for normal vision. Genetic models, such as knockout mice, are valuable for studying its functions.

In a consanguineous Pakistani family, a missense mutation in GNAT1 (p.D129G) was associated with autosomal recessive stationary night blindness, and Gnat1 was predominantly expressed in the retina [1]. A novel homozygous truncating mutation in GNAT1 was reported in a patient with retinitis pigmentosa, suggesting some truncating GNAT1 variants can cause a recessive, mild, late-onset retinal degeneration in addition to night-blindness [2]. In Gnat1-/-mice, constitutively depolarized rods release excessive glutamate, accelerating deep plexus angiogenesis and paracellular blood-retinal barrier maturation, indicating its role in regulating these retinal processes [3]. Also, in Gnat1-/-; Gnat2cpfl3/cpfl3 double-knockout mice, which lack rod and cone photoresponses, there were still robust light-induced visual cortex evoked potentials, suggesting a role for melanopsin-mediated phototransduction in pattern-forming vision [4].

In conclusion, GNAT1 is essential for rod phototransduction, and its proper function is crucial for normal vision. Mutations in GNAT1 are associated with retinal disorders like congenital stationary night blindness and retinitis pigmentosa. Studies using Gnat1 knockout mouse models have revealed its roles in retinal angiogenesis, blood-retinal barrier maturation, and the contribution of melanopsin-mediated phototransduction to pattern-forming vision.

References:

1. Naeem, Muhammad Asif, Chavali, Venkata R M, Ali, Shahbaz, Hejtmancik, J Fielding, Riazuddin, S Amer. 2012. GNAT1 associated with autosomal recessive congenital stationary night blindness. In Investigative ophthalmology & visual science, 53, 1353-61. doi:10.1167/iovs.11-8026. https://pubmed.ncbi.nlm.nih.gov/22190596/

2. Carrigan, Matthew, Duignan, Emma, Humphries, Pete, Kenna, Paul F, Farrar, G Jane. 2015. A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration. In The British journal of ophthalmology, 100, 495-500. doi:10.1136/bjophthalmol-2015-306939. https://pubmed.ncbi.nlm.nih.gov/26472407/

3. Biswas, Saptarshi, Shahriar, Sanjid, Bachay, Galina, Brunken, William J, Agalliu, Dritan. 2024. Glutamatergic neuronal activity regulates angiogenesis and blood-retinal barrier maturation via Norrin/β-catenin signaling. In Neuron, 112, 1978-1996.e6. doi:10.1016/j.neuron.2024.03.011. https://pubmed.ncbi.nlm.nih.gov/38599212/

4. Flood, Michael D, Veloz, Hannah L B, Hattar, Samer, Carvalho-de-Souza, Joao L. 2022. Robust visual cortex evoked potentials (VEP) in Gnat1 and Gnat2 knockout mice. In Frontiers in cellular neuroscience, 16, 1090037. doi:10.3389/fncel.2022.1090037. https://pubmed.ncbi.nlm.nih.gov/36605613/