Slc38a8, a solute carrier family 38 member 8, is a putative glutamine transporter. It facilitates glutamine influx, which converts to glutamate in the visual pathway [2]. Mutations in this gene are associated with FHONDA syndrome, a subtype of foveal hypoplasia with congenital nystagmus and optic-nerve-decussation defects without pigmentation leading to severe vision loss [2]. Mouse models, generated using Nuclease technology technology, have been crucial for studying Slc38a8. Slc38a8 mutant mice exhibit wild-type eye and coat pigmentation but show subcellular abnormalities in retinal pigment epithelium cells, reduction of ipsilateral retinal fibers, decreased electroretinography (ERG) response in scotopic conditions, and reduced visual acuity [1]. These phenotypes recapitulate the characteristics of FHONDA patients, indicating normal pigmentation and abnormal visual systems [1].

In addition, in vitro studies on retinal cell lines overexpressing SLC38A8 show that its overexpression influences retinal gene expression, light detection, visual perception, as well as glutamine and glutamate dynamics [2]. In vivo, Slc38a8-truncated gene mice display altered testicular morphology, degenerative changes in germinal epithelium, elevated liver enzyme, and enhanced scotopic responsiveness in electroretinogram [2].

In conclusion, Slc38a8 plays a vital role in retinal function and glutamine-glutamate metabolism. The Slc38a8-KO mouse models have significantly contributed to understanding the pathophysiology of FHONDA syndrome, providing insights into the role of Slc38a8 in the development of the visual pathway and associated diseases [1,2].

References:

1. Guardia, Ana, Fernández, Almudena, Seruggia, Davide, Cuenca, Nicolás, Montoliu, Lluís. . A Slc38a8 Mouse Model of FHONDA Syndrome Faithfully Recapitulates the Visual Deficits of Albinism Without Pigmentation Defects. In Investigative ophthalmology & visual science, 64, 32. doi:10.1167/iovs.64.13.32. https://pubmed.ncbi.nlm.nih.gov/37862028/

2. Weiner, Chen, Hecht, Idan, Lindovsky, Jiri, Shomron, Noam, Pras, Eran. 2025. Characterisation of SLC38A8 and Its Role in Retinal Pathways and Disease. In Clinical & experimental ophthalmology, , . doi:10.1111/ceo.14504. https://pubmed.ncbi.nlm.nih.gov/39956648/