--This initial study found evidence linking changes in organ development with symptoms seen in certain human mitochondrial diseases --

--这项初步研究发现，器官发育的变化与某些人类线粒体疾病的症状有关--

PHILADELPHIA, Sept. 20, 2023 /PRNewswire/ -- Zebrafish have revolutionized research into a wide variety of rare and complex genetic diseases. In early development stages, their transparent bodies allow researchers to more easily study tissues and organs. However, studying organ-level defects in adult zebrafish presents a variety of challenges that prevent researchers from studying them at a microscopic level..

费城，2023年9月20日/PRNewswire/-斑马鱼已经彻底改变了对各种罕见和复杂遗传疾病的研究。在早期发育阶段，它们的透明身体使研究人员能够更容易地研究组织和器官。然而，研究成年斑马鱼的器官水平缺陷提出了各种挑战，阻止研究人员在微观水平上研究它们。。

In a new study, researchers from Children's Hospital of Philadelphia (CHOP) have developed a noninvasive method for conducting magnetic resonance imaging (MRI) in adult zebrafish. Using this technique, the study team examined the effects of certain genetic mutations associated with mitochondrial disease..

在一项新研究中，费城儿童医院（CHOP）的研究人员开发了一种非侵入性方法，用于在成年斑马鱼中进行磁共振成像（MRI）。使用这项技术，研究小组检查了与线粒体疾病相关的某些基因突变的影响。。

The findings were recently published online by the journal Zebrafish.

这些发现最近由Zebrafish杂志在线发表。

Zebrafish transition from a single cell to fully formed animal in just one day, with continued larval development over the first week of life. This rapid development and ability to remove their body wall pigment during this early period enables scientists to microscopically image whole organs and perform accurate time-lapse analyses of disease progression.

斑马鱼在短短一天内从单个细胞过渡到完全形成的动物，并在生命的第一周继续幼虫发育。在这个早期阶段，这种快速发展和去除体壁色素的能力使科学家能够对整个器官进行显微镜成像，并对疾病进展进行准确的延时分析。

They can also screen drug candidates that may be used to treat various illnesses, since the zebrafish can absorb the drug through their gut, skin, or thin gills. In addition, zebrafish are often used to create models to study diseases because zebrafish share about 70% of genes found in humans..

由于斑马鱼可以通过肠道，皮肤或细鳃吸收药物，因此它们还可以筛选可用于治疗各种疾病的候选药物。此外，斑马鱼通常用于创建研究疾病的模型，因为斑马鱼共享人类中约70%的基因。。

However, as zebrafish get older, their tissue becomes denser and their organs become more difficult to study through usual microscopic imaging techniques. While MRI has been used to study zebrafish, prior studies have been very limited and did not provide systematic organ-level analyses. This is particularly important for diseases like mitochondrial disease, which often impacts multiple organs by disrupting energy levels in cells throughout the body.

然而，随着斑马鱼年龄的增长，它们的组织变得更加密集，并且通过通常的显微成像技术研究它们的器官变得更加困难。虽然MRI已被用于研究斑马鱼，但先前的研究非常有限，并未提供系统的器官水平分析。这对于像线粒体疾病这样的疾病尤其重要，线粒体疾病通常通过破坏整个身体细胞的能量水平来影响多个器官。

No prior study studied adult zebrafish across different times in their adulthood, which prevented researchers from looking into the progression of disease..

之前没有研究在成年期不同时间研究成年斑马鱼，这阻止了研究人员研究疾病的进展。。

'MRI technology is widely used for a variety of clinical and research applications, and as zebrafish become a more preferred model for translational research, we wanted to explore how this technology could improve the research we are doing in these animal models,' said first study author Sonal Sharma, MD, a pediatric neurologist within the Division of Neurology and the Mitochondrial Medicine Frontier Program in the Division of Human Genetics at CHOP.

“MRI技术被广泛应用于各种临床和研究应用，随着斑马鱼成为转化研究的首选模型，我们想探索这项技术如何改善我们在这些动物模型中所做的研究，”第一研究作者Sonal Sharma博士说，CHOP人类遗传学系神经内科和线粒体医学前沿计划的儿科神经科医生。

'This work demonstrated that MRI allows us to rapidly and comprehensively study organ-level growth defects in mutant adult zebrafish in a low-cost, minimally invasive, and unbiased manner.'.

“这项工作表明，MRI使我们能够以低成本，微创和无偏见的方式快速全面地研究突变成年斑马鱼的器官水平生长缺陷。”。

The researchers developed a new protocol for utilizing MRI in zebrafish research. As a result, they were able to successfully capture high-resolution MRI of eight different organs in adult zebrafish. This allowed the researchers to establish a reference MRI atlas based on images of zebrafish from five to 31 months after fertilization..

研究人员开发了一种在斑马鱼研究中利用MRI的新方案。结果，他们能够成功捕获成年斑马鱼中八个不同器官的高分辨率MRI。这使得研究人员能够根据受精后5到31个月的斑马鱼图像建立参考MRI图谱。。

Using three different mitochondrial disease mutant models of zebrafish, the researchers were able to discover that significantly increased brain growth occurs in zebrafish with deficiency in the SURF1 gene, which encode mitochondrial complex IV activity and is one of the genes associated with Leigh syndrome.

使用三种不同的斑马鱼线粒体疾病突变模型，研究人员能够发现，SURF1基因缺乏的斑马鱼大脑生长显着增加，SURF1基因编码线粒体复合物IV活性，并且是与Leigh综合征相关的基因之一。

They also noticed heart and spinal cord volumes were smaller in these mutant zebrafish as compared to healthy wild-type controls. These findings reflect some of the clinical observations seen in human patients with SURF1 deficiency, since they may suffer from serious neurological issues as well as cardiomyopathy..

他们还注意到，与健康的野生型对照相比，这些突变斑马鱼的心脏和脊髓体积较小。这些发现反映了SURF1缺乏症患者的一些临床观察，因为他们可能患有严重的神经系统问题以及心肌病。。

'We plan on exploring the organ-level discoveries we made by using this novel MRI method to screen organ growth in adult zebrafish,' said senior study author Marni Falk, MD, senior author on this study and executive director of the Mitochondrial Medicine Frontier Program at CHOP. 'We are also working to develop additional biochemical imaging methods to further refine our understanding of the biochemical changes that occur in specific organs of living animals with primary mitochondrial disease.'.

高级研究作者Marni Falk博士，本研究高级作者和线粒体医学前沿项目执行主任说：“我们计划探索我们通过使用这种新型MRI方法筛选成年斑马鱼器官生长所取得的器官水平发现。”CHOP'我们还在努力开发其他生化成像方法，以进一步完善我们对原发性线粒体疾病活体动物特定器官中发生的生化变化的理解。

This study was supported by the Children's Hospital of Philadelphia Mitochondrial Medicine Fellowship Program and the National Institutes of Health grant R35-GM134863.

这项研究得到了费城儿童医院线粒体医学研究金计划和美国国立卫生研究院R35-GM134863的支持。

Sharma et al, 'Novel Development of Magnetic Resonance Imaging to Quantify the Structural Anatomic Growth of Diverse Organs in Adult and Mutant Zebrafish.' Zebrafish. Online August 21, 2023. DOI: 10.1089/zeb.2023.0018.

Sharma等人，“磁共振成像的新发展，以量化成年和突变斑马鱼中不同器官的结构解剖生长”斑马鱼。在线2023年8月21日。DOI:10.1089/zeb.2023.0018。

About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the 595-bed hospital has fostered many discoveries that have benefited children worldwide.

关于费城儿童医院：费城儿童医院是一家非营利性慈善组织，成立于1855年，是全国第一家儿科医院。通过长期致力于提供卓越的患者护理，培训新一代儿科医疗保健专业人员以及开创性的重大研究举措，拥有595张床位的医院培养了许多有益于全球儿童的发现。

Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as an inpatient hospital with a dedicated pediatric emergency department in King of Prussia.

其儿科研究计划是该国最大的项目之一。该机构通过其CHOP护理网络在家附近提供先进的儿科护理已有悠久的历史，其中包括宾夕法尼亚州和新泽西州的50多种初级保健实践，专科护理和外科中心，紧急护理中心和社区医院联盟，以及在普鲁士国王设有专门儿科急诊科的住院医院。

In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit https://www.chop.edu. .

此外，其独特的以家庭为中心的护理和公共服务计划使费城儿童医院成为儿童和青少年的主要倡导者。欲了解更多信息，请访问https://www.chop.edu. .

Contact: Ben LeachChildren's Hospital of Philadelphia(609)634-7906[email protected]

联系方式：费城Ben LeachChildren医院（609）634-7906[电子邮件保护]

SOURCE Children's Hospital of Philadelphia

费城儿童医院