雪貂模型及其在生物医学研究中的应用

doi:10.19586/j.2095-2341.2025.0053

生物技术进展 ›› 2025, Vol. 15 ›› Issue (5): 812-818.DOI: 10.19586/j.2095-2341.2025.0053

雪貂模型及其在生物医学研究中的应用

武旭(), 潘文韬(), 彭瑾瑜(), 李钰玮, 张嘉轩, 刘婉婧, 吕佳杭, 高鑫源(), 隋宏书(), 柴迪硕()

山东第一医科大学临床与基础医学院，济南 250117

收稿日期:2025-04-21 接受日期:2025-06-06 出版日期:2025-09-25 发布日期:2025-11-11
通讯作者: 高鑫源,隋宏书,柴迪硕
作者简介:武旭 E-mail: 2683927158@qq.com；
潘文韬 E-mail: wentaopan021107@163.com
彭瑾瑜 E-mail: 3369960246@qq.com第一联系人：并列第一作者
基金资助:
国家自然科学基金项目(81670004);山东第一医科大学校级大学生创新创业训练项目(2024104390742);山东第一医科大学教育教学改革项目(JXGGYJ-2224325)

The Ferret Models and its Application in Biomedicine Research

Xu WU(), Wentao PAN(), Jinyu PENG(), Yuwei LI, Jiaxuan ZHANG, Wanjing LIU, Jiahang LYU, Xinyuan GAO(), Hongshu SUI(), Dishuo CHAI()

College of Clinical and Basic Medicine，Shandong First Medical University，Jinan 250117，China

Received:2025-04-21 Accepted:2025-06-06 Online:2025-09-25 Published:2025-11-11
Contact: Xinyuan GAO,Hongshu SUI,Dishuo CHAI

摘要/Abstract

摘要：

雪貂因其与人类在解剖和生理上的相似性，尤其是呼吸系统和神经系统，使其成为跨学科生物医学研究的理想模型。近年来，基因组编辑技术的进步使得高效创建基因修饰雪貂成为可能，极大地拓宽了其在基础和转化研究中的应用。雪貂的生物学特性使其在实验适用性与物种代表性层面达到了双重优化，填补了啮齿类动物和非人灵长类动物模型的空白。综述重点介绍了雪貂独特的生物学特性及其在模拟人类病原体感染、呼吸系统和神经系统疾病以及啮齿类动物模型无法有效复制的复杂疾病中的应用，讨论了与雪貂研究相关的挑战及未来提升其应用价值的方向，旨在增进对人类疾病的理解和扩展新型疗法的开发。

关键词: 雪貂, 生物医学研究, 基因组编辑, 疾病模型

Abstract:

Domestic ferrets have become a valuable model in interdisciplinary biomedical research due to their anatomical and physiological similarities to humans， particularly in the respiratory and nervous systems. These characteristics enable ferrets to address critical research questions that rodent models cannot adequately resolve. Recent advancements in genome editing technology have made it possible to efficiently create genetically modified ferrets， significantly expanding their applications in both basic and translational studies. Ferrets strike a balance between practicality and biological relevance， bridging the gap between rodent and non-human primate models. This review highlighted the unique biological features of ferrets and their utility in modeling human pathogen infections， respiratory and neurological disorders， as well as complex diseases that are poorly replicated in rodent models. It discussed challenges associated with ferret research and outline future directions to enhance their value， aiming to advance the understanding of human diseases and expand the development of novel therapeutics.

Key words: ferrets, biomedical research, genome editing, disease models

中图分类号:

Q95-3

武旭, 潘文韬, 彭瑾瑜, 李钰玮, 张嘉轩, 刘婉婧, 吕佳杭, 高鑫源, 隋宏书, 柴迪硕. 雪貂模型及其在生物医学研究中的应用[J]. 生物技术进展, 2025, 15(5): 812-818.

Xu WU, Wentao PAN, Jinyu PENG, Yuwei LI, Jiaxuan ZHANG, Wanjing LIU, Jiahang LYU, Xinyuan GAO, Hongshu SUI, Dishuo CHAI. The Ferret Models and its Application in Biomedicine Research[J]. Current Biotechnology, 2025, 15(5): 812-818.

参考文献 48

[1]	HOPPES S M. The senior ferret (Mustela putorius furo)[J]. Vet. Clin. North Am. Exot. Anim. Pract., 2010, 13(1): 107-122.
[2]	GRUNTMAN A M, FLOTTE T R. Gene therapy and the use of animal models: why mice alone are not sufficient[J]. Hum. Gene Ther., 2022, 33(9-10): 477-478.
[3]	PHILLIPS K A, BALES K L, CAPITANIO J P, et al.. Why primate models matter[J]. Am. J. Primatol., 2014, 76(9): 801-827.
[4]	WONG J, LAYTON D, WHEATLEY A K, et al.. Improving immunological insights into the ferret model of human viral infectious disease[J]. Influenza Other Respir. Viruses, 2019, 13(6): 535-546.
[5]	IBRICEVIC A, PEKOSZ A, WALTER M J, et al.. Influenza virus receptor specificity and cell tropism in mouse and human airway epithelial cells[J]. J. Virol., 2006, 80(15): 7469-7480.
[6]	PULIT-PENALOZA J A, BELSER J A, BROCK N, et al.. Transmission of a human isolate of clade 2.3.4.4b A(H5N1) virus in ferrets[J]. Nature, 2024, 636(8043): 705-710.
[7]	PULIT-PENALOZA J A, BROCK N, BELSER J A, et al.. Highly pathogenic avian influenza A(H5N1) virus of clade 2.3.4.4b isolated from a human case in Chile causes fatal disease and transmits between co-housed ferrets[J/OL]. Emerg. Microbes Infect., 2024, 13(1): 2332667[2025-06-06]. .
[8]	KIM Y I, KIM S G, KIM S M, et al.. Infection and rapid transmission of SARS-CoV-2 in ferrets[J]. Cell Host Microbe, 2020, 27(5): 704-709.
[9]	KIM Y I, YU K M, YKOH J, et al.. Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets[J/OL]. Nat. Commun., 2022, 13(1): 21[2025-06-06]. .
[10]	GUPTA T, SOMANNA N, ROWE T, et al.. Ferrets as a model for tuberculosis transmission[J/OL]. Front. Cell. Infect. Microbiol., 2022, 12: 873416[2025-06-06]. .
[11]	HUSSAIN S S, EDWARDS Y J K, LIBBY E F, et al.. Comparative transcriptomics in human COPD reveals dysregulated genes uniquely expressed in ferrets[J/OL]. Respir. Res., 2022, 23(1): 277[2025-06-06]. .
[12]	PEABODY L J E, LI Q, PAVELKOVA N, et al.. Pulmonary fibrosis ferret model demonstrates sustained fibrosis, restrictive physiology, and aberrant repair[J/OL]. BioRxiv, 2024: 2024.06.04.597198[2025-06-06]. .
[13]	KHOURY O, CLOUSE C, MCSWAIN M K, et al.. Ferret acute lung injury model induced by repeated nebulized lipopolysaccharide administration[J/OL]. Physiol. Rep., 2022, 10(20): e15400[2025-06-06].
[14]	WU C, CHEN X, CAI Y, et al.. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China[J]. JAMA Intern. Med., 2020, 180(7): 934-943.
[15]	AIZAWA K, LIU C, VEERAMACHANENI S, et al.. Development of ferret as a human lung cancer model by injecting 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK)[J]. Lung Cancer, 2013, 82(3): 390-396.
[16]	FOX J G, OTTO G, TAYLOR N S, et al.. Helicobacter mustelae-induced gastritis and elevated gastric pH in the ferret (Mustela putorius furo)[J]. Infect. Immun., 1991, 59(6): 1875-1880.
[17]	FOX J G, CORREA P, TAYLOR N S, et al.. Helicobacter mustelae-associated gastritis in ferrets. An animal model of Helicobacter pylori gastritis in humans[J]. Gastroenterology. 1990, 99(2): 352-61.
[18]	PATTERSON M M, O'TOOLE P W, FORESTER N T, et al.. Failure of surface ring mutant strains of Helicobacter mustelae to persistently infect the ferret stomach[J]. Infect. Immun., 2003, 71(5): 2350-2355.
[19]	O'TOOLE P W, SNELLING W J, CANCHAYA C, et al.. Comparative genomics and proteomics of Helicobacter mustelae, an ulcerogenic and carcinogenic gastric pathogen[J/OL]. BMC Genomics, 2010, 11: 164[2025-06-06]. .
[20]	FOX J G, DANGLER C A, SAGER W, et al.. Helicobacter mustelae-associated gastric adenocarcinoma in ferrets (Mustela putorius furo)[J]. Vet. Pathol., 1997, 34(3): 225-229.
[21]	GOINEAU S, ROMPION S, GUILLAUME P, et al.. Using telemetry to Automate the detection of Emesis in the ferret: new vistas for delayed Emesis assessment[J]. J. Pharmacol. Toxicol. Methods, 2013, 68(1): 160-165.
[22]	LEMPEL A A, NIELSEN K J. Ferrets as a model for higher-level visual motion processing[J]. Curr. Biol., 2019, 29(2): 179-191.
[23]	MEDINA A E, FOXWORTHY W A, KEUM D, et al.. Development of multisensory processing in ferret parietal cortex[J]. Eur. J. Neurosci., 2023, 58(5): 3226-3238.
[24]	JOSHI N, NG W Y, THAKKAR K, et al.. Temporal coherence shapes cortical responses to speech mixtures in a ferret cocktail party[J/OL]. Commun. Biol., 2024, 7(1): 1392[2025-06-06]. .
[25]	JACKSON C A, PEDUZZI J D, HICKEY T L. Visual cortex development in the ferret. I. genesis and migration of visual cortical neurons[J]. J. Neurosci., 1989, 9(4): 1242-1253.
[26]	SAWADA K, WATANABE M. Development of cerebral sulci and gyri in ferrets (Mustela putorius)[J]. Congenit. Anomalies, 2012, 52(3): 168-175.
[27]	GILARDI C, KALEBIC N. The ferret as a model system for neocortex development and evolution[J/OL]. Front. Cell Dev. Biol., 2021, 9: 661759[2025-06-06]. .
[28]	MAJKOWSKI J. Drug effects on afterdischarge and seizure threshold in lissencephalic ferrets: an epilepsy model for drug evaluation[J]. Epilepsia, 1983, 24(6): 678-685.
[29]	SCHWERIN S C, CHATTERJEE M, IMAM-FULANI A O, et al.. Progression of histopathological and behavioral abnormalities following mild traumatic brain injury in the male ferret[J]. J. Neurosci. Res., 2018, 96(4): 556-572.
[30]	HASLING T A, GIERDALSKI M, JABLONSKA B, et al.. A radialization factor in normal cortical plate restores disorganized radial Glia and disrupted migration in a model of cortical dysplasia[J]. Eur. J. Neurosci., 2003, 17(3): 467-480.
[31]	SCHWERIN S C, HUTCHINSON E B, RADOMSKI K L, et al.. Establishing the ferret as a gyrencephalic animal model of traumatic brain injury: optimization of controlled cortical impact procedures[J]. J. Neurosci. Methods, 2017, 285: 82-96.
[32]	GOODFELLOW M J, HONG L E, PISKOUN B, et al.. Behavioral assessment of well-being in the naïve laboratory ferret (Mustela putorius furo)[J/OL]. Sci. Rep., 2024, 14(1): 30119[2025-06-06]. .
[33]	JIMENEZ I A, CRANEY M C, PAINTER M C, et al.. Behavioral evaluation of laboratory-housed ferrets (Mustela putorius furo) in different enclosure sizes[J]. J. Am. Assoc. Lab. Anim. Sci., 2023, 62(5): 382-394.
[34]	MUZUMDAR M D, TASIC B, MIYAMICHI K, et al.. A global double-fluorescent Cre reporter mouse[J]. Genesis, 2007, 45(9): 593-605.
[35]	HAYASHI S, MCMAHON A P. Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse[J]. Dev. Biol., 2002, 244(2): 305-318.
[36]	YU M, SUN X, TYLER S R, et al.. Highly efficient transgenesis in ferrets using CRISPR/Cas9-mediated homology-independent insertion at the ROSA26 locus[J/OL]. Sci. Rep., 2019, 9(1): 1971[2025-06-06]. .
[37]	YUAN F, GASSER G N, LEMIRE E, et al.. Transgenic ferret models define pulmonary ionocyte diversity and function[J]. Nature, 2023, 621(7980): 857-867.
[38]	高维崧,窦金萍,韦双,等.CRISPR/Cas系统的分类及研究现状[J].生物技术进展,2022,12(4):532-538.
	GAO W S, DOU J P, WEI S, et al.. Classification and research status of CRISPR/cas systems[J]. Curr. Biotechnol., 2022, 12(4): 532-538.
[39]	王阿利,刘江东.CRISPR/Cas系统在斑马鱼中的研究进展[J].生物技术进展,2023,13(4):485-491.
	WANG A L, LIU J D. Research progress on the CRISPR/Cas system in zebrafish[J]. Curr. Biotechnol., 2023, 13(4): 485-491.
[40]	张笑天,王智,朱鹏宇,等.一种基于定量PCR的CRISPR/Cas9基因编辑作物快速检测方法的研究[J].生物技术进展,2023,13(6):907-912.
	ZHANG X T, WANG Z, ZHU P Y, et al.. A rapid detection method based on qPCR for CRISPR/Cas9 edited crops[J]. Curr. Biotechnol., 2023, 13(6): 907-912.
[41]	ROMMENS J M, IANNUZZI M C, KEREM B, et al.. Identification of the cystic fibrosis gene: chromosome walking and jumping[J]. Science, 1989, 245(4922): 1059-1065.
[42]	STOLTZ D A, MEYERHOLZ D K, WELSH M J. Origins of cystic fibrosis lung disease[J]. N. Engl. J. Med., 2015, 372(16): 1574-1575.
[43]	王泓恺,王俞杰,赵潇涵,等.囊性纤维化基因治疗研究进展[J].生物技术进展,2024,14(5):813-819.
	WANG H K, WANG Y J, ZHAO X H, et al.. Research progress on cystic fibrosis gene therapy[J]. Curr. Biotechnol., 2024, 14(5): 813-819.
[44]	SUN X, YAN Z, YI Y, et al.. Adeno-associated virus-targeted disruption of the CFTR gene in cloned ferrets[J]. J. Clin. Invest., 2008, 118(4): 1578-1583.
[45]	SUN X, OLIVIER A K, LIANG B, et al.. Lung phenotype of juvenile and adult cystic fibrosis transmembrane conductance regulator-knockout ferrets[J]. Am. J. Respir. Cell Mol. Biol., 2014, 50(3): 502-512.
[46]	EVANS I A, SUN X, LIANG B, et al.. In utero and postnatal ivacaftor/lumacaftor therapy rescues multiorgan disease in CFTR-F508del ferrets[J/OL]. JCI Insight, 2024, 9(8): e157229[2025-06-06]. .
[47]	JOHNSON M B, SUN X, KODANI A, et al.. Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size[J]. Nature, 2018, 556(7701): 370-375.
[48]	WANG W, YIN C, WEN S, et al.. DCX knockout ferret reveals a neurogenic mechanism in cortical development[J/OL]. Cell Rep., 2024, 43(8): 114508[2025-06-06]. .

雪貂模型及其在生物医学研究中的应用

The Ferret Models and its Application in Biomedicine Research

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 48

相关文章 2

编辑推荐

Metrics

本文评价

[1]	王阿利, 刘江东. CRISPR/Cas系统在斑马鱼中的研究进展[J]. 生物技术进展, 2023, 13(4): 485-491.
[2]	郑小梅,张晓立,于建东,郑平,孙际宾,. CRISPR-Cas9介导的基因组编辑技术的研究进展[J]. 生物技术进展, 2015, 5(1): 1-9.