Erin K Touchette, Maria C Bates, Mitch C Johnson, Tracy C O'Brien, Roger J Melton, Kelly R Long, Masakazu Kakuni, Matthew Baginski, Daniel R Radiloff, John E Sagartz
{"title":"人源化肝脏嵌合小鼠维生素C缺乏症的特征及预防。","authors":"Erin K Touchette, Maria C Bates, Mitch C Johnson, Tracy C O'Brien, Roger J Melton, Kelly R Long, Masakazu Kakuni, Matthew Baginski, Daniel R Radiloff, John E Sagartz","doi":"10.30802/AALAS-CM-22-000027","DOIUrl":null,"url":null,"abstract":"<p><p>Humanized liver chimeric mice (PXB-mice) are generated by the transplantation of human hepatocytes into mice that have severe combined immunodeficiency and express an albumin-promoted urokinase-type plasminogen activator (cDNA-uPA/SCID) transgene. Human hepatocytes cannot synthesize ascorbic acid (AA; commonly called vitamin C) and humans require supplementation to prevent vitamin C deficiency. PXB-mouse livers contain up to approximately 95% human hepatocytes, which likely affects AA synthesis. To determine whether dietary AA supplementation prevents scurvy-like symptoms and death in PXB-mice, a 12 week study that compared nonsupplemented and supplemented PXB-mice was conducted. Approximately 4 weeks into the study, PXB-mice without dietary supplementation of AA displayed weight loss and clinical signs of hypovitaminosis C, including hunched posture, unkempt appearance, and lameness. Pathologic evaluation of nonsupplemented PXB-mice revealed lesions consistent with hypovitaminosis C. Mean serum AA concentrations in the nonsupplemented PXB-mice were below the limit of quantitation (0.5 μg/mL) and were substantially less than those of controls. AA was also measured in a number of tissues, including adrenal gland, brain, liver, and testis; low AA concentrations were similarly observed in tissues obtained from the nonsupplemented PXB-mice. Collectively, these findings support AA supplementation in PXB-mice to prevent the development of hypovitaminosis C and the potential utility of nonsupplemented PXB-mice as an animal model of scurvy.</p>","PeriodicalId":10659,"journal":{"name":"Comparative medicine","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9827606/pdf/cm2022000355.pdf","citationCount":"1","resultStr":"{\"title\":\"Characterization and Prevention of Hypovitaminosis C in Chimeric Mice with Humanized Livers.\",\"authors\":\"Erin K Touchette, Maria C Bates, Mitch C Johnson, Tracy C O'Brien, Roger J Melton, Kelly R Long, Masakazu Kakuni, Matthew Baginski, Daniel R Radiloff, John E Sagartz\",\"doi\":\"10.30802/AALAS-CM-22-000027\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Humanized liver chimeric mice (PXB-mice) are generated by the transplantation of human hepatocytes into mice that have severe combined immunodeficiency and express an albumin-promoted urokinase-type plasminogen activator (cDNA-uPA/SCID) transgene. Human hepatocytes cannot synthesize ascorbic acid (AA; commonly called vitamin C) and humans require supplementation to prevent vitamin C deficiency. PXB-mouse livers contain up to approximately 95% human hepatocytes, which likely affects AA synthesis. To determine whether dietary AA supplementation prevents scurvy-like symptoms and death in PXB-mice, a 12 week study that compared nonsupplemented and supplemented PXB-mice was conducted. Approximately 4 weeks into the study, PXB-mice without dietary supplementation of AA displayed weight loss and clinical signs of hypovitaminosis C, including hunched posture, unkempt appearance, and lameness. Pathologic evaluation of nonsupplemented PXB-mice revealed lesions consistent with hypovitaminosis C. Mean serum AA concentrations in the nonsupplemented PXB-mice were below the limit of quantitation (0.5 μg/mL) and were substantially less than those of controls. AA was also measured in a number of tissues, including adrenal gland, brain, liver, and testis; low AA concentrations were similarly observed in tissues obtained from the nonsupplemented PXB-mice. Collectively, these findings support AA supplementation in PXB-mice to prevent the development of hypovitaminosis C and the potential utility of nonsupplemented PXB-mice as an animal model of scurvy.</p>\",\"PeriodicalId\":10659,\"journal\":{\"name\":\"Comparative medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2022-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9827606/pdf/cm2022000355.pdf\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Comparative medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.30802/AALAS-CM-22-000027\",\"RegionNum\":4,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"VETERINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Comparative medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.30802/AALAS-CM-22-000027","RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
Characterization and Prevention of Hypovitaminosis C in Chimeric Mice with Humanized Livers.
Humanized liver chimeric mice (PXB-mice) are generated by the transplantation of human hepatocytes into mice that have severe combined immunodeficiency and express an albumin-promoted urokinase-type plasminogen activator (cDNA-uPA/SCID) transgene. Human hepatocytes cannot synthesize ascorbic acid (AA; commonly called vitamin C) and humans require supplementation to prevent vitamin C deficiency. PXB-mouse livers contain up to approximately 95% human hepatocytes, which likely affects AA synthesis. To determine whether dietary AA supplementation prevents scurvy-like symptoms and death in PXB-mice, a 12 week study that compared nonsupplemented and supplemented PXB-mice was conducted. Approximately 4 weeks into the study, PXB-mice without dietary supplementation of AA displayed weight loss and clinical signs of hypovitaminosis C, including hunched posture, unkempt appearance, and lameness. Pathologic evaluation of nonsupplemented PXB-mice revealed lesions consistent with hypovitaminosis C. Mean serum AA concentrations in the nonsupplemented PXB-mice were below the limit of quantitation (0.5 μg/mL) and were substantially less than those of controls. AA was also measured in a number of tissues, including adrenal gland, brain, liver, and testis; low AA concentrations were similarly observed in tissues obtained from the nonsupplemented PXB-mice. Collectively, these findings support AA supplementation in PXB-mice to prevent the development of hypovitaminosis C and the potential utility of nonsupplemented PXB-mice as an animal model of scurvy.
期刊介绍:
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.