Mouse and non-human primate models of neurodegenerative disease：The prevalence of age-related neurodegenerative diseases continues to increase with ever increasing aging population over the age of 60.Although the dif...Mouse and non-human primate models of neurodegenerative disease：The prevalence of age-related neurodegenerative diseases continues to increase with ever increasing aging population over the age of 60.Although the difficulties associated with neurodegenerative diseases present an urgent global issue,there is no effective treatment for these conditions.展开更多
The common marmoset (Callithrix jacchus), a small new world monkey species, has been widely used in various scientific fields. It is necessary to understand connections between specific genotypes, their structure, and...The common marmoset (Callithrix jacchus), a small new world monkey species, has been widely used in various scientific fields. It is necessary to understand connections between specific genotypes, their structure, and function;however, an anatomical atlas of the entire body of the common marmoset has not yet been reported. In addition to conventional absorption, refraction enhanced computed tomography (CT) based on synchrotron radiation can increase the contrast of boundaries between small absorption differences. In this study, to examine the potential of creating an anatomical atlas of the whole body of the common marmoset non-invasively, we visualized an intact marmoset using synchrotron refraction enhanced CT. The cryogenic marmoset was scanned using the medical imaging beamline at the SPring-8 synchrotron radiation research facility in JAPAN. The trabecular structure, articular cartilage, cruciate ligament in the knee joint, and small airways (diameter: > 400 μm) was clearly identified with 50 μm voxel size and 37 keV x-ray energy. The structure of the heart and branching vessels in the kidneys and liver were also identified without contrast agents, and the anatomical structure of the brain was slightly visible. These results show that synchrotron refraction enhanced CT is useful for creating an anatomical atlas non-invasively, and further studies are planned that will combine refraction enhanced CT and other imaging techniques to analyse the morphology and create a complete atlas of the whole body of the common marmoset.展开更多
Patients with Philadelphia chromosome (p190 BCR-ABL fusion gene)-positive acute lymphoblastic leukemia have a poor prognosis despite intensive therapeutic intervention.In this study, we attempted to develop a leukemia...Patients with Philadelphia chromosome (p190 BCR-ABL fusion gene)-positive acute lymphoblastic leukemia have a poor prognosis despite intensive therapeutic intervention.In this study, we attempted to develop a leukemia nonhuman primate model that mimics various human systems. Hematopoietic stem/progenitor cells in the common marmoset were transduced with a lentiviral vector containing the p190 BCR-ABL fusion gene by ex vivo transduction or in vivo direct bone marrow injection. In the latter model, BCR-ABL gene expression was maintained for more than one and a half years. One marmoset unexpectedly developed myelofibrosis-like disease. However, none of the marmosets have developed leukemia to date. In conclusion, we successfully achieved sustained p190 BCR-ABL gene expression in vivo. However, a genetic mutation in addition to p190 BCR-ABL may be required for the malignant transformation of hematopoietic stem/progenitor cells in the common marmoset during the short observation period. This novel in vivo approach will help develop a marmoset leukemia model in the future.展开更多
The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independ...The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independently reported in two Asian primate research centers.Nevertheless,the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated.Here,we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing.We identified 14558184 single nucleotide polymorphisms(SNPs)from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples.Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers.In addition,SNP and copy number variation(CNV)analyses suggested that the WW domain-containing oxidoreductase(WWOX)and Tyrosine-protein phosphatase nonreceptor type 21(PTPN21)genes may be associated with epilepsy in marmosets.Notably,KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets.This study provides valuable population genomic resources for marmosets in two Asian primate centers.Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers,while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.展开更多
Much has been written about hepatic metastasis and animal models abound. In terms of the human experience, progress in treating this final common pathway, a terminal event of many human malignancies has been relativel...Much has been written about hepatic metastasis and animal models abound. In terms of the human experience, progress in treating this final common pathway, a terminal event of many human malignancies has been relatively slow. The current thinking is that primary prevention is best served by early detection of cancer and eradication of early stage cancers by screening. Some cancers spread early in their course and the role of screening may be limited. Until relatively recently there has not been a pathfinder model that makes the evasion of this unfortunate event a reality. This review discusses such an animal model and attempts to relate it to human disease in terms of intervention. Concrete proposals are also offered on how scientists may be able to intervene to prevent this deadly progression of the cancer process.展开更多
文摘Mouse and non-human primate models of neurodegenerative disease：The prevalence of age-related neurodegenerative diseases continues to increase with ever increasing aging population over the age of 60.Although the difficulties associated with neurodegenerative diseases present an urgent global issue,there is no effective treatment for these conditions.
文摘The common marmoset (Callithrix jacchus), a small new world monkey species, has been widely used in various scientific fields. It is necessary to understand connections between specific genotypes, their structure, and function;however, an anatomical atlas of the entire body of the common marmoset has not yet been reported. In addition to conventional absorption, refraction enhanced computed tomography (CT) based on synchrotron radiation can increase the contrast of boundaries between small absorption differences. In this study, to examine the potential of creating an anatomical atlas of the whole body of the common marmoset non-invasively, we visualized an intact marmoset using synchrotron refraction enhanced CT. The cryogenic marmoset was scanned using the medical imaging beamline at the SPring-8 synchrotron radiation research facility in JAPAN. The trabecular structure, articular cartilage, cruciate ligament in the knee joint, and small airways (diameter: > 400 μm) was clearly identified with 50 μm voxel size and 37 keV x-ray energy. The structure of the heart and branching vessels in the kidneys and liver were also identified without contrast agents, and the anatomical structure of the brain was slightly visible. These results show that synchrotron refraction enhanced CT is useful for creating an anatomical atlas non-invasively, and further studies are planned that will combine refraction enhanced CT and other imaging techniques to analyse the morphology and create a complete atlas of the whole body of the common marmoset.
文摘Patients with Philadelphia chromosome (p190 BCR-ABL fusion gene)-positive acute lymphoblastic leukemia have a poor prognosis despite intensive therapeutic intervention.In this study, we attempted to develop a leukemia nonhuman primate model that mimics various human systems. Hematopoietic stem/progenitor cells in the common marmoset were transduced with a lentiviral vector containing the p190 BCR-ABL fusion gene by ex vivo transduction or in vivo direct bone marrow injection. In the latter model, BCR-ABL gene expression was maintained for more than one and a half years. One marmoset unexpectedly developed myelofibrosis-like disease. However, none of the marmosets have developed leukemia to date. In conclusion, we successfully achieved sustained p190 BCR-ABL gene expression in vivo. However, a genetic mutation in addition to p190 BCR-ABL may be required for the malignant transformation of hematopoietic stem/progenitor cells in the common marmoset during the short observation period. This novel in vivo approach will help develop a marmoset leukemia model in the future.
基金supported by the National Natural Science Foundation of China (82001372)National Key Research and Development Program of China (2018YFE0126700)+3 种基金Shanghai Jiao Tong University 2030 Initiative (WH510363001-7)Shanghai Municipal Commission of Science and Technology Program (21dz2210100)Shanghai Education Commission Research and Innovation Program (2019-01-07-00-02-E00037)a National Institutes of Health (NIH)grant (5R01HG002385)to E.E.E。
文摘The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independently reported in two Asian primate research centers.Nevertheless,the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated.Here,we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing.We identified 14558184 single nucleotide polymorphisms(SNPs)from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples.Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers.In addition,SNP and copy number variation(CNV)analyses suggested that the WW domain-containing oxidoreductase(WWOX)and Tyrosine-protein phosphatase nonreceptor type 21(PTPN21)genes may be associated with epilepsy in marmosets.Notably,KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets.This study provides valuable population genomic resources for marmosets in two Asian primate centers.Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers,while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.
文摘Much has been written about hepatic metastasis and animal models abound. In terms of the human experience, progress in treating this final common pathway, a terminal event of many human malignancies has been relatively slow. The current thinking is that primary prevention is best served by early detection of cancer and eradication of early stage cancers by screening. Some cancers spread early in their course and the role of screening may be limited. Until relatively recently there has not been a pathfinder model that makes the evasion of this unfortunate event a reality. This review discusses such an animal model and attempts to relate it to human disease in terms of intervention. Concrete proposals are also offered on how scientists may be able to intervene to prevent this deadly progression of the cancer process.
