Document Detail

The Tsukuba hypertensive mouse (transgenic mouse carrying human genes for both renin and angiotensinogen) as a model of human malignant hypertension: development of lesions and morphometric analysis.
MedLine Citation:
PMID:  9504863     Owner:  NLM     Status:  MEDLINE    
The renin-angiotensin system has a pivotal role in hypertension. The Tsukuba hypertensive mouse (THM; a transgenic mouse carrying human genes for both renin and angiotensinogen) was generated to allow further examination of the renin-angiotensin system in a variety of pathologic conditions. We evaluated the development of renal lesions in these mice and in controls by morphometric, immunohistochemical and ultrastructural methods. Blood pressure was significantly higher in THM than in control mice; 1 year after birth, it was approximately 40 mmHg higher. The kidney-to-body weight ratio was also higher in THM than in control. Morphometrical analysis revealed that the glomerular sclerosis index was significantly elevated in THM with 10% of the glomeruli sclerotic at 18 months. The grade of vascular lesion and the frequency of fibronoid arteritis of the kidney exhibited the same tendency as the glomerular sclerosis index. Murine renin was located exclusively in the juxtaglomerular apparatus, whereas human renin was expressed not only in the juxtaglomerular apparatus, but also in periarteriolar smooth muscle cells and in mesangial and epithelial cells of the glomeruli. Light and electron microscopy revealed significant fibrinoid arteritis of the kidney in THM and also "onion skinning", both pathognomonic for malignant nephrosclerosis. THM may be an excellent model of human malignant hypertension.
T Shimokama; S Haraoka; H Horiguchi; F Sugiyama; K Murakami; T Watanabe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Virchows Archiv : an international journal of pathology     Volume:  432     ISSN:  0945-6317     ISO Abbreviation:  Virchows Arch.     Publication Date:  1998 Feb 
Date Detail:
Created Date:  1998-03-26     Completed Date:  1998-03-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9423843     Medline TA:  Virchows Arch     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  169-75     Citation Subset:  IM    
Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
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MeSH Terms
Arteritis / pathology
Blood Pressure / physiology
Disease Models, Animal
Endothelium / ultrastructure
Glomerulosclerosis, Focal Segmental / genetics,  pathology
Hypertension* / genetics,  pathology,  physiopathology
Juxtaglomerular Apparatus / metabolism,  pathology
Kidney Glomerulus / blood supply,  pathology*
Mice, Transgenic / genetics*,  physiology
Muscle, Smooth, Vascular / ultrastructure
Renin-Angiotensin System / genetics*,  physiology

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