Ubiquitous Luciferase Expression in “Firefly Rats” Does Not Alter the Pancreatic Islet Morphology, Metabolism, and Function
“Firefly rats” ubiquitously express the luciferase reporter gene under the control of constitutively active ROSA26 promoter in inbred Lewis rats. Due to the minimal immunogenicity of luciferase, wide applications of Firefly rats have been reported in solid organ/cell transplantation studies for in v...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2023-06-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/09636897231182497 |
| _version_ | 1827914905755320320 |
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| author | Nelson Gonzalez Hiroyuki Kato Wilma Tixi Jose Ortiz Chris Orr Hung-Ping Shih Hsun Teresa Ku Jiing-Kuan Yee Fouad Kandeel Yoko Mullen Eiji Kobayashi Hirotake Komatsu |
| author_facet | Nelson Gonzalez Hiroyuki Kato Wilma Tixi Jose Ortiz Chris Orr Hung-Ping Shih Hsun Teresa Ku Jiing-Kuan Yee Fouad Kandeel Yoko Mullen Eiji Kobayashi Hirotake Komatsu |
| author_sort | Nelson Gonzalez |
| collection | DOAJ |
| description | “Firefly rats” ubiquitously express the luciferase reporter gene under the control of constitutively active ROSA26 promoter in inbred Lewis rats. Due to the minimal immunogenicity of luciferase, wide applications of Firefly rats have been reported in solid organ/cell transplantation studies for in vivo imaging, permitting quantitative and non-invasive tracking of the transplanted graft. ROSA26 is a non-coding gene and generally does not affect the expression of other endogenous genes. However, the effect of ubiquitous luciferase expression on islet morphology and function has not been thoroughly investigated, which is critical for the use of Firefly rats as islet donors in islet transplantation studies. Accordingly, in vivo glucose homeostasis (i.e., islet function in the native pancreas) was compared between age-matched luciferase-expressing Firefly rats and non-luciferase-expressing rats. In vivo assessments demonstrated no statistical difference between these rats in non-fasting blood glucose levels, intraperitoneal glucose tolerance tests, and glucose-stimulated serum C-peptide levels. Furthermore, islets were isolated from both rats to compare the morphology, function, and metabolism in vitro . Isolated islets from both rats exhibited similar in vitro characteristics in post-isolation islet yield, islet size, beta cell populations, insulin content per islet, oxygen consumption rate, and glucose-stimulated insulin secretion. In conclusion, ubiquitous luciferase expression in Firefly rats does not affect their islet morphology, metabolism, and function; this finding is critical and enables the use of isolated islets from Firefly rats for the dual assessment of islet graft function and bioluminescence imaging of islet grafts. |
| first_indexed | 2024-03-13T02:51:55Z |
| format | Article |
| id | doaj.art-d9939e4fbe0148df8740c480b1a26889 |
| institution | Directory Open Access Journal |
| issn | 1555-3892 |
| language | English |
| last_indexed | 2024-03-13T02:51:55Z |
| publishDate | 2023-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-d9939e4fbe0148df8740c480b1a268892023-06-28T11:33:19ZengSAGE PublishingCell Transplantation1555-38922023-06-013210.1177/09636897231182497Ubiquitous Luciferase Expression in “Firefly Rats” Does Not Alter the Pancreatic Islet Morphology, Metabolism, and FunctionNelson Gonzalez0Hiroyuki Kato1Wilma Tixi2Jose Ortiz3Chris Orr4Hung-Ping Shih5Hsun Teresa Ku6Jiing-Kuan Yee7Fouad Kandeel8Yoko Mullen9Eiji Kobayashi10Hirotake Komatsu11Department of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA, USADepartment of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA, USADepartment of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA, USADepartment of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA, USADepartment of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA, USADepartment of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA, USADepartment of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA, USADepartment of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA, USADepartment of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA, USADepartment of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA, USADepartment of Kidney Regenerative Medicine, The Jikei University School of Medicine, Tokyo, JapanDepartment of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA, USA“Firefly rats” ubiquitously express the luciferase reporter gene under the control of constitutively active ROSA26 promoter in inbred Lewis rats. Due to the minimal immunogenicity of luciferase, wide applications of Firefly rats have been reported in solid organ/cell transplantation studies for in vivo imaging, permitting quantitative and non-invasive tracking of the transplanted graft. ROSA26 is a non-coding gene and generally does not affect the expression of other endogenous genes. However, the effect of ubiquitous luciferase expression on islet morphology and function has not been thoroughly investigated, which is critical for the use of Firefly rats as islet donors in islet transplantation studies. Accordingly, in vivo glucose homeostasis (i.e., islet function in the native pancreas) was compared between age-matched luciferase-expressing Firefly rats and non-luciferase-expressing rats. In vivo assessments demonstrated no statistical difference between these rats in non-fasting blood glucose levels, intraperitoneal glucose tolerance tests, and glucose-stimulated serum C-peptide levels. Furthermore, islets were isolated from both rats to compare the morphology, function, and metabolism in vitro . Isolated islets from both rats exhibited similar in vitro characteristics in post-isolation islet yield, islet size, beta cell populations, insulin content per islet, oxygen consumption rate, and glucose-stimulated insulin secretion. In conclusion, ubiquitous luciferase expression in Firefly rats does not affect their islet morphology, metabolism, and function; this finding is critical and enables the use of isolated islets from Firefly rats for the dual assessment of islet graft function and bioluminescence imaging of islet grafts.https://doi.org/10.1177/09636897231182497 |
| spellingShingle | Nelson Gonzalez Hiroyuki Kato Wilma Tixi Jose Ortiz Chris Orr Hung-Ping Shih Hsun Teresa Ku Jiing-Kuan Yee Fouad Kandeel Yoko Mullen Eiji Kobayashi Hirotake Komatsu Ubiquitous Luciferase Expression in “Firefly Rats” Does Not Alter the Pancreatic Islet Morphology, Metabolism, and Function Cell Transplantation |
| title | Ubiquitous Luciferase Expression in “Firefly Rats” Does Not Alter the Pancreatic Islet Morphology, Metabolism, and Function |
| title_full | Ubiquitous Luciferase Expression in “Firefly Rats” Does Not Alter the Pancreatic Islet Morphology, Metabolism, and Function |
| title_fullStr | Ubiquitous Luciferase Expression in “Firefly Rats” Does Not Alter the Pancreatic Islet Morphology, Metabolism, and Function |
| title_full_unstemmed | Ubiquitous Luciferase Expression in “Firefly Rats” Does Not Alter the Pancreatic Islet Morphology, Metabolism, and Function |
| title_short | Ubiquitous Luciferase Expression in “Firefly Rats” Does Not Alter the Pancreatic Islet Morphology, Metabolism, and Function |
| title_sort | ubiquitous luciferase expression in firefly rats does not alter the pancreatic islet morphology metabolism and function |
| url | https://doi.org/10.1177/09636897231182497 |
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