Department of Physiology, Faculty of Medicine, University of Iceland, 101 Reykjavík, Iceland.
Department of Ophthalmology, Landspitali-National University Hospital, 101 Reykjavík, Iceland.
Genes (Basel). 2023 Jul 17;14(7):1458. doi: 10.3390/genes14071458.
Mutations in the mouse microphthalmia-associated transcription factor () gene affect retinal pigment epithelium (RPE) differentiation and development and can lead to hypopigmentation, microphthalmia, deafness, and blindness. For instance, an association has been established between loss-of-function mutations in the mouse gene and a variety of human retinal diseases, including Waardenburg type 2 and Tietz syndromes. Although there is evidence showing that mice with the homozygous mutation manifest microphthalmia and osteopetrosis, there are limited or no data on the effects of the heterozygous condition in the eye. mice can therefore be regarded as an important model system for the study of human disease. Thus, we characterized mice at 1, 3, 12, and 18 months old in comparison with age-matched wild-type mice. The light- and dark-adapted electroretinogram (ERG) recordings showed progressive cone-rod dystrophy in mice. The RPE response was reduced in the mutant in all age groups studied. Progressive loss of pigmentation was found in mice. Histological retinal sections revealed evidence of retinal degeneration in mice at older ages. For the first time, we report a mouse model of progressive cone-rod dystrophy and RPE dysfunction with a mutation in the gene.
突变的小鼠小眼相关转录因子（）基因影响视网膜色素上皮（RPE）分化和发育，并可导致色素减退、小眼、耳聋和失明。例如，在小鼠基因的功能丧失性突变与多种人类视网膜疾病之间建立了关联，包括沃登伯格综合征 2 型和泰茨综合征。尽管有证据表明，具有纯合突变的小鼠表现出小眼和骨硬化症，但在眼部中，关于杂合状态的影响的数据有限或没有。因此，小鼠可以被视为研究人类疾病的重要模型系统。因此，我们对 1、3、12 和 18 个月大的与年龄匹配的野生型小鼠进行了特征描述。明、暗适应的视网膜电图（ERG）记录显示，小鼠中进行性的锥杆细胞营养不良。在所有研究的年龄组中，突变体的 RPE 反应均降低。在小鼠中发现色素沉着逐渐丧失。组织学视网膜切片显示，在较老的年龄，小鼠中存在视网膜变性的证据。我们首次报道了一种具有基因突变的进行性锥杆细胞营养不良和 RPE 功能障碍的小鼠模型。
