Imperial College London
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ProfessorFrederickTam

Faculty of Medicine, Department of Immunology and Inflammation

Ken and Mary Minton Chair of Renal Medicine
 
 
 
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Contact

 

+44 (0)20 3313 2354f.tam

 
 
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Location

 

9N, 15C, Commonwealth BuildingHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Falcone:2019:10.1038/s41598-019-56837-6,
author = {Falcone, S and Wisby, L and Nicol, T and Blease, A and Starbuck, B and Parker, A and Sanderson, J and Brown, SDM and Scudamore, CL and Pusey, C and Tam, F and Potter, PK},
doi = {10.1038/s41598-019-56837-6},
journal = {Scientific Reports},
title = {Modification of an aggressive model of Alport Syndrome reveals early differences in disease pathogenesis due to genetic background},
url = {http://dx.doi.org/10.1038/s41598-019-56837-6},
volume = {9},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The link between mutations in collagen genes and the development of Alport Syndromehas been clearly established and a number of animal models, including knock-out mouselines, have been developed that mirror disease observed in patients. However, it is clearfrom both patients and animal models that the progression of disease can vary greatlyand can be modified genetically. We have identified a point mutation in Col4a4 in micewhere disease is modified by strain background, providing further evidence of thegenetic modification of disease symptoms. Our results indicate that C57BL/6J is aprotective background and postpones end stage renal failure from 7 weeks, as seen on aC3H background, to several months. We have identified early differences in diseaseprogression, including expression of podocyte-specific genes and podocyte morphology.In C57BL/6J mice podocyte effacement is delayed, prolonging normal renal function.The slower disease progression has allowed us to begin dissecting the pathogenesis ofmurine Alport Syndrome in detail. We find that there is evidence of differential geneexpression during disease on the two genetic backgrounds, and that disease diverges by4 weeks of age. We also show that an inflammatory response with increasing MCP-1 andKIM-1 levels precedes loss of renal function.
AU  - Falcone,S
AU  - Wisby,L
AU  - Nicol,T
AU  - Blease,A
AU  - Starbuck,B
AU  - Parker,A
AU  - Sanderson,J
AU  - Brown,SDM
AU  - Scudamore,CL
AU  - Pusey,C
AU  - Tam,F
AU  - Potter,PK
DO  - 10.1038/s41598-019-56837-6
PY  - 2019///
SN  - 2045-2322
TI  - Modification of an aggressive model of Alport Syndrome reveals early differences in disease pathogenesis due to genetic background
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-019-56837-6
UR  - http://hdl.handle.net/10044/1/75496
VL  - 9
ER  -
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