title: The commonly used beta-actin-GFP transgenic mouse strain develops a distinct type of glomerulosclerosis.
abstract: 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.
authors.affiliation: Section of Nephrology, Department of Internal Medicine, Yale School of Medicine, 333 Cedar St, P.O. Box 208029, New Haven, CT 06520, USA. jiankan.guo@yale.edu
authors.forename: Jian-Kan
authors.initials: JK
authors.lastname: Guo
authors.forename: Ee-Chun
authors.initials: EC
authors.lastname: Cheng
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: E Scott
authors.initials: ES
authors.lastname: Swenson
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Ardito
authors.forename: Michael
authors.initials: M
authors.lastname: Kashgarian
authors.forename: Lloyd G
authors.initials: LG
authors.lastname: Cantley
authors.forename: Diane S
authors.initials: DS
authors.lastname: Krause
mesh_terms: D000199:Actins / Q000235:genetics*; D000818:Animals; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional
chemical_list: D000199:Actins; D049452:Green Fluorescent Proteins