The commonly used β-actin-GFP transgenic mouse strain develops a distinct type of glomerulosclerosis
Autor: | Ee-chun Cheng, Michael Kashgarian, Lloyd G. Cantley, Thomas Ardito, Lin Wang, E. Scott Swenson, Diane S. Krause, Jian-Kan Guo |
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Rok vydání: | 2007 |
Předmět: |
Genetically modified mouse
medicine.diagnostic_test Glomerulosclerosis Focal Segmental Transgene Glomerular basement membrane Green Fluorescent Proteins Mice Transgenic Promoter Biology Molecular biology Actins Green fluorescent protein Mice Inbred C57BL Insertional mutagenesis Mice Mutagenesis Insertional medicine.anatomical_structure Western blot Genetics medicine Animals Animal Science and Zoology Ubiquitin C Agronomy and Crop Science Biotechnology |
Zdroj: | Transgenic Research. 16:829-834 |
ISSN: | 1573-9368 0962-8819 |
DOI: | 10.1007/s11248-007-9107-x |
Popis: | Green fluorescent protein (GFP) transgenic animals are widely used in biomedical research. We observed that the commonly used beta-actin-GFP transgenic mouse has renal defects with proteinuria starting as early as 5 weeks of age. Histological analysis reveals a widespread increase in glomerular extracellular matrix, occasional mesangiolysis, and secondary tubulointerstitial injury. Electron microscopic (EM) analysis reveals dramatic thickening of the glomerular basement membrane (GBM). Several other transgenic strains with GFP on ubiquitous promoters including beta-actin (with insertion in a different location) and ubiquitin C show no renal abnormalities. Western blot analysis on crude glomerular preparations from several GFP transgenic strains revealed that higher levels of GFP expression might be responsible for the observed pathogenesis. Mapping of the transgene insertion site by inverse PCR indicates that the beta-actin GFP transgene does not cause insertional mutagenesis nor does it modify the transcription level of adjacent genes. Taken together, this strain of beta-actin-GFP transgenic mouse may be used to study the mechanism of GBM expansion. Moreover, experiments using this strain of GFP mouse should be hereafter carefully planned because its renal pathology may interfere with data interpretation. |
Databáze: | OpenAIRE |
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