HBS1L 缺乏症会导致儿童视网膜营养不良,小鼠模型与感光细胞发育缺陷有关。

IF 4 3区 医学 Q2 CELL BIOLOGY
Disease Models & Mechanisms Pub Date : 2024-08-01 Epub Date: 2024-07-30 DOI:10.1242/dmm.050557
Shiyu Luo, Bilal Alwattar, Qifei Li, Kiran Bora, Alexandra K Blomfield, Jasmine Lin, Anne Fulton, Jing Chen, Pankaj B Agrawal
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引用次数: 0

摘要

遗传性视网膜疾病是由对视网膜功能至关重要的基因突变引起的一组遗传性疾病,其中包括一些核糖体相关基因。本研究的重点是 HBS1L 基因,该基因编码对核糖体救援至关重要的 HBS1-like 翻译 GTPase。我们曾报道过一名携带双倍拷贝 HBS1L 变体的女性患儿,其表现为生长发育不良和神经发育迟缓。在此,我们描述了该患者和 Hbs1ltm1a/tm1a 低倍型小鼠的眼科发现,并描述了相关的显微和分子扰动。患者的视觉功能受损,在杆状波和锥体介导的反应中,a 波和 b 波的振幅减弱。由于大量感光细胞凋亡,Hbs1ltm1a/tm1a 小鼠的整个视网膜,特别是外感光层严重变薄。质谱分析显示,HBS1L 的缺失导致了蛋白质组的全面改变,169 种蛋白质增加,480 种蛋白质减少,其中包括视紫红质和周边蛋白 2。这些发现强调了核糖体拯救蛋白在维持视网膜健康,尤其是感光细胞健康方面的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
HBS1L deficiency causes retinal dystrophy in a child and in a mouse model associated with defective development of photoreceptor cells.

Inherited retinal diseases encompass a genetically diverse group of conditions caused by variants in genes critical to retinal function, including handful of ribosome-associated genes. This study focuses on the HBS1L gene, which encodes for the HBS1-like translational GTPase that is crucial for ribosomal rescue. We have reported a female child carrying biallelic HBS1L variants, manifesting with poor growth and neurodevelopmental delay. Here, we describe the ophthalmologic findings in the patient and in Hbs1ltm1a/tm1a hypomorph mice and describe the associated microscopic and molecular perturbations. The patient has impaired visual function, showing dampened amplitudes of a- and b-waves in both rod- and cone-mediated responses. Hbs1ltm1a/tm1a mice exhibited profound thinning of the entire retina, specifically of the outer photoreceptor layer, due to extensive photoreceptor cell apoptosis. Loss of Hbs1l resulted in comprehensive proteomic alterations by mass spectrometry analysis, with an increase in the levels of 169 proteins and a decrease in the levels of 480 proteins, including rhodopsin (Rho) and peripherin 2 (Prph2). Gene Ontology biological process and gene set enrichment analyses reveal that the downregulated proteins are primarily involved in phototransduction, cilium assembly and photoreceptor cell development. These findings underscore the importance of ribosomal rescue proteins in maintaining retinal health, particularly in photoreceptor cells.

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来源期刊
Disease Models & Mechanisms
Disease Models & Mechanisms 医学-病理学
CiteScore
6.60
自引率
7.00%
发文量
203
审稿时长
6-12 weeks
期刊介绍: Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.
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