Novel Development of Magnetic Resonance Imaging to Quantify the Structural Anatomic Growth of Diverse Organs in Adult and Mutant Zebrafish.

IF 1.4 4区生物学 Q4 DEVELOPMENTAL BIOLOGY

Zebrafish Pub Date : 2024-02-01 Epub Date: 2023-08-21 DOI:10.1089/zeb.2023.0018

Sonal Sharma, Sergey Magnitsky, Emily Reesey, Mitchell Schwartz, Suraiya Haroon, Manuela Lavorato, Sherine Chan, Rui Xiao, Benjamin J Wilkins, Daniel Martinez, Christoph Seiler, Marni J Falk

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Abstract

Zebrafish (Danio rerio) is a widely used vertebrate animal for modeling genetic diseases by targeted editing strategies followed by gross phenotypic and biomarker characterization. While larval transparency permits microscopic detection of anatomical defects, histological adult screening for organ-level defects remains invasive, tedious, inefficient, and subject to technical artifact. Here, we describe a noninvasive magnetic resonance imaging (MRI) approach to systematically screen adult zebrafish for anatomical growth defects. An anatomical atlas of wild-type (WT) zebrafish at 5-31 months post-fertilization was created by ex vivo MRI with a 9.4 T magnet. Volumetric growth over time was measured of animals and major organs, including the brain, spinal cord, heart, eyes, optic nerve, ear, liver, kidneys, and swim bladder. Subsequently, surf1^-/-, fbxl4^-/-, and opa1^+/- mitochondrial disease mutant adult zebrafish were quantitatively studied to compare organ volumes with age-matched WT zebrafish. Results demonstrated that MRI enabled noninvasive, high-resolution, rapid screening of mutant adult zebrafish for overall and organ-specific growth abnormalities. Detailed volumetric analyses of three mitochondrial disease mutants delineated specific organ differences, including significantly increased brain growth in surf1^-/- and opa1^+/-, and marginally significant decreased heart and spinal cord volumes in surf1^-/- mutants. This is interesting as we know neurological involvement can be seen in SURF1^-^/- patients with ataxia, dystonia, and lesions in basal ganglia, as well as in OPA1^+/- patients with spasticity, ataxia, and hyperreflexia indicative of neuropathology. Similarly, cardiomyopathy is a known sequelae of cardiac pathology in patients with SURF1^-^/--related disease. Future studies will define MRI signaling patterns of organ dysfunction to further delineate specific pathology.

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磁共振成像在量化成年斑马鱼和变异斑马鱼不同器官的结构解剖生长方面的新进展。

斑马鱼（Danio rerio）是一种广泛应用的脊椎动物，通过靶向编辑策略建立遗传疾病模型，然后进行粗略的表型和生物标记表征。虽然幼体透明度允许显微镜检测解剖学缺陷，但组织学成体器官水平缺陷筛查仍然是侵入性的、繁琐的、低效的，并受技术假象的影响。在这里，我们描述了一种无创磁共振成像（MRI）方法，用于系统筛查成年斑马鱼的解剖生长缺陷。利用 9.4 T 磁体进行体外磁共振成像，绘制了野生型（WT）斑马鱼受精后 5-31 个月的解剖图谱。测量了动物和主要器官（包括大脑、脊髓、心脏、眼睛、视神经、耳朵、肝脏、肾脏和膀胱）随时间增长的体积。随后，对surf1-/-、fbxl4-/-和opa1+/-线粒体疾病突变成年斑马鱼进行了定量研究，以比较与年龄匹配的WT斑马鱼的器官体积。结果表明，核磁共振成像可对突变成年斑马鱼的整体和器官特异性生长异常进行无创、高分辨率的快速筛查。对三种线粒体疾病突变体的详细容积分析划定了特定器官的差异，包括surf1-/-和opa1+/-的大脑生长显著增加，而surf1-/-突变体的心脏和脊髓体积略有显著减少。这一点很有意思，因为我们知道神经系统受累可见于共济失调、肌张力障碍和基底神经节病变的 SURF1-/- 患者，也可见于痉挛、共济失调和反射亢进的 OPA1+/- 患者，这些都是神经病理学的表现。同样，已知心肌病是SURF1-/-相关疾病患者心脏病变的后遗症。未来的研究将确定器官功能障碍的核磁共振成像信号模式，以进一步划分特定病理。

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来源期刊

Zebrafish DEVELOPMENTAL BIOLOGY-ZOOLOGY

CiteScore

3.60

自引率

5.00%

发文量

审稿时长

3 months

期刊介绍： Zebrafish is the only peer-reviewed journal dedicated to the central role of zebrafish and other aquarium species as models for the study of vertebrate development, evolution, toxicology, and human disease. Due to its prolific reproduction and the external development of the transparent embryo, the zebrafish is a prime model for genetic and developmental studies. While genetically more distant from humans, the vertebrate zebrafish nevertheless has comparable organs and tissues, such as heart, kidney, pancreas, bones, and cartilage. Zebrafish introduced the new section TechnoFish, which highlights these innovations for the general zebrafish community. TechnoFish features two types of articles: TechnoFish Previews: Important, generally useful technical advances or valuable transgenic lines TechnoFish Methods: Brief descriptions of new methods, reagents, or transgenic lines that will be of widespread use in the zebrafish community Zebrafish coverage includes: Comparative genomics and evolution Molecular/cellular mechanisms of cell growth Genetic analysis of embryogenesis and disease Toxicological and infectious disease models Models for neurological disorders and aging New methods, tools, and experimental approaches Zebrafish also includes research with other aquarium species such as medaka, Fugu, and Xiphophorus.