DOI: 10.1002/ame2.70051
Comparative analysis of two newly established Cre rat lines,NeuN-Cre and Thy1-Cre,for neurological research
Keru Li1
Chenyang Liu1
Gefan Wan1
Lei Zhang1
Rui Fan2
Xu Zhang3
Yuanlong Su2
Jiayue He1
Ning Liu3
Feifei Guan1
Wei Dong3
Shan Gao3
Weining Kong3
Xiaolong Qi3
Xiaolin Zhang4
Yuanwu Ma5
1.State Key Laboratory of Respiratory Health and Multimorbidity,NHC Key Laboratory of Human Disease Comparative Medicine,Key Laboratory of Pathogen Infection Prevention and Control,Ministry of Education,National Human Diseases Animal Model Resource Center and National Center of Technology Innovation for Animal Model,Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences(CAMS),Peking Union Medical College(PUMC),Beijing,China2.State Key Laboratory of Vascular Homeostasis and Remodeling,Institute of Cardiovascular Sciences,School of Basic Medical Sciences,Peking University,Beijing,China3.State Key Laboratory of Respiratory Health and Multimorbidity,NHC Key Laboratory of Human Disease Comparative Medicine,Key Laboratory of Pathogen Infection Prevention and Control,Ministry of Education,National Human Diseases Animal Model Resource Center and National Center of Technology Innovation for Animal Model,Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences(CAMS),Peking Union Medical College(PUMC),Beijing,China;Haihe Laboratory of Cell Ecosystem,Tianjin,China4.The Second Affiliated Hospital of Chengdu Medical College,China National Nuclear Corporation 416 Hospital,Chengdu,China5.State Key Laboratory of Respiratory Health and Multimorbidity,NHC Key Laboratory of Human Disease Comparative Medicine,Key Laboratory of Pathogen Infection Prevention and Control,Ministry of Education,National Human Diseases Animal Model Resource Center and National Center of Technology Innovation for Animal Model,Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences(CAMS),Peking Union Medical College(PUMC),Beijing,China;Haihe Laboratory of Cell Ecosystem,Tianjin,China;Medical Primate Research Center and Neuroscience Center,Chinese Academy of Medical Sciences,Beijing,China
摘要：Background:The Cre/loxP system is most popular in mice,but its application in rats has largely lagged far behind.The rat is vital laboratory animal,especially in toxico-logical and neurological studies.Generating genetic tools to manipulate neurons in rats could benefit neurological research.
Methods:Using the CRISPR/Cas9 system,we inserted a Cre cassette into endog-enous Thy1 and NeuN loci.Thy1-Cre rats featured a downstream P2A-linked insertion,while NeuN-Cre was inserted at the transcriptional start site.The Cre activity was assessed by crossing with a Cre reporter(Rosa26'mCherry)rat and through analyzing mCherry expression patterns.The specificity of cell type was further confirmed by immunofluorescence with NeuN antibody.Phenotypic consequences were assessed by crossing with ND1LSL rats to deplete ND1,followed by monitoring weight/survival and conducting motor function tests.
Results:We generated two neuron-specific rats(Thy1-Cre and NeuN-Cre),which ex-hibited high neuron-specific Cre expression in brain and spinal cord with minor leak-age in other tissues.Thy1-Cre showed minor leakage in spleen,lung and kidney while NeuN-Cre showed minor leakage in spleen and kidney.ND1Thy1-Cre and ND1NeuNCre rats both showed decreased body weights and survival times.The ND1NeuN-Cre rats died within two weeks,while ND1Thy1-Cre rats lived longer with impaired motor function.
Conclusions:We successfully generated two neuron-specific NeuN-Cre and Thy1-Cre rats,and systemically analyzed their expression pattern.
机标关键词：researchanalysislinescomparativeestablishedneun-creneurologicalnewly
论文发表日期：2025-08-30
在线出版日期：2025-11-05（本平台首次上网日期，不代表文献的发表时间）
页数：12( 1468-1479 )
英文信息