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This multiorgan disorder results from inactivating point mutations in either the TSC1 or the TSC2 genes and consequent activation of the canonical mammalian target of rapamycin complex 1 signalling (mTORC1) pathway. Since lesions to the eye are central to TSC diagnosis, we report here the generation and characterisation of the first eye-specific TSC mouse model. We demonstrate that conditional ablation of Tsc1 in eye committed progenitor cells leads to the accelerated differentiation and subsequent ectopic radial migration of retinal ganglion cells. This results in an increase in retinal ganglion cell apoptosis and consequent regionalized axonal loss within the optic nerve and topographical changes to the contra- and ipsilateral input within the dorsal lateral geniculate nucleus. Eyes from adult mice exhibit aberrant retinal architecture and display all the classic neuropathological hallmarks of TSC including an increase in organ and cell size, ring heterotopias, hamartomas with retinal detachment and lamination defects. Our results provide the first major insight into the molecular etiology of TSC within the developing eye and demonstrate a pivotal role for Tsc1 in regulating various aspects of visual pathway development. Our novel mouse model therefore provides a valuable resource for future studies concerning the molecular mechanisms underlying TSC and also as a platform to evaluate new therapeutic approaches for the treatment of this multiorgan disorder.<\/jats:p>","DOI":"10.1242\/dmm.021972","type":"journal-article","created":{"date-parts":[[2015,10,9]],"date-time":"2015-10-09T01:28:52Z","timestamp":1444354132000},"source":"Crossref","is-referenced-by-count":8,"title":["A novel mouse model of Tuberous Sclerosis Complex (TSC): eye-specific <i>Tsc1<\/i>-ablation disrupts visual pathway development"],"prefix":"10.1242","author":[{"given":"Iwan","family":"Jones","sequence":"first","affiliation":[{"name":"Ume\u00e5 Center for Molecular Medicine (UCMM), Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Carin","family":"H\u00e4gglund","sequence":"additional","affiliation":[{"name":"Ume\u00e5 Center for Molecular Medicine (UCMM), Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunilla","family":"T\u00f6rnqvist","sequence":"additional","affiliation":[{"name":"Ume\u00e5 Center for Molecular Medicine (UCMM), Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoffer","family":"Nord","sequence":"additional","affiliation":[{"name":"Ume\u00e5 Center for Molecular Medicine (UCMM), Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Ahlgren","sequence":"additional","affiliation":[{"name":"Ume\u00e5 Center for Molecular Medicine (UCMM), Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif","family":"Carlsson","sequence":"additional","affiliation":[{"name":"Ume\u00e5 Center for Molecular Medicine (UCMM), Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042513094421900_DMM021972C1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ydbio.2007.01.045","article-title":"Molecular mechanisms of optic vesicle development: complexities, ambiguities and controversies","volume":"305","author":"Adler","year":"2007","journal-title":"Dev. 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