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Renal Proteomics in Rodent Meckel Gruber Syndrome
Author(s) -
Gattone Vincent,
Mason Stephen,
Witzmann Frank,
Ringham Heather,
Lai Xian Yin
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.739.24
Subject(s) - azotemia , biology , uremia , proteome , phenotype , disease , pathology , proteomics , medicine , endocrinology , bioinformatics , gene , genetics , renal function
Wpk rats are a viable model for human Meckel Gruber syndrome (MKS), allowing a disease stage proteomic analysis of renal tissue. We hypothesize there are differentially expressed proteins associated with the inherited cystic trait and others associated with renal dysfunction in the later stage. These represent both mechanistic and diagnostic biomarkers for disease inheritance and progression. Wistar‐Wpk/Wpk rats are compared with intralitter normals at 10 days (early stage disease) and 21 days (late stage). Rats were anesthetized; kidneys flushed with 0.9% saline, and frozen in liquid nitrogen until all specimens were collected. Kidneys were homogenized in IPG (urea, diothiotreitol, and CHAPS) solution and 750 ug of protein was loaded for 2‐D electrophoresis. The stained gels were analyzed with Progenesis SameSpots software (Nonlinear Dynamics, Ltd.) which identified a total of 72 spots with a statistically different, normalized staining intensity in at least one group. We identified five distinctly interpretable patterns of protein expression which identify changes associated with cystic phenotype and disease progression/azotemia. Pattern 1 reflects proteins elevated while Pattern 2 reflects proteins decreased in cystic disease. Pattern 3 reflects proteins that are enhanced in cystic disease, but increase with the extent of the cysts. Patterns 4 are proteins that are increased in late stage cystic disease. Pattern 5 reflects proteins down regulated in response to the uremia. Selected spots/proteins which match these patterns are analyzed by LC‐MS/MS. The Wpk model of MKS presents an interesting study in differential protein expression. Characterization of protein changes may provide insight into the mechanisms of renal cyst development and lead to diagnostic biomarkers of disease progression.