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suPAR in diabetic complications: Establishing a suPAR overexpressing mouse model
Summary Data Summary
Applicant Holzman, Lawrence
E-Mail Address lholzman@upenn.edu
Project Title suPAR in diabetic complications: Establishing a suPAR overexpressing mouse model
CBU ID 12GHSU203
External SubContract ID 25034-20
Diabetic Complication Nephropathy
Funding Program Group Pilot & Feasibility [PF2012]
Abstract Epidemiological studies suggest that elevated soluble urokinase plasminogen
activator receptor (suPAR) concentration in plasma and urine are associated with
increased risk of cardiovascular diseases (CVD), Type 2 diabetes, and cancer.
Although these studies suggest that increased suPAR concentration might predict
risk of presenting with these pathologies, suPAR’s role in disease pathogenesis
remains unclear. The possibility that suPAR either is causative for or
contributes to disease pathogenesis was recently suggested by Wei et al. who
reported that administration of suPAR to mice resulted in proteinuria and focal
and segmental glomerular histopathology. While these observations require
validation, they provide rationale for the hypothesis that chronically increased
suPAR might contribute directly to the pathogenesis of diabetic complications
including its cardiovascular complications or diabetic nephropathy. Here we
propose developing models to test this hypothesis directly by creating and
initially characterizing transgenic mouse models in which suPAR protein is
over-expressed from liver in an inducible fashion. GPI-linked
membrane-associated uPAR undergoes proteolytic cleavage to produce soluble
proteolytic products detectable in blood and urine. Because one cannot predict a
priori which product is functionally relevant, two mouse models will be created,
one expressing suPAR protein containing all three suPAR ectodomains and one
expressing only domains II and III. Following validation, these mouse lines will
be employed to examine the hypothesis that suPAR induces a FSGS phenotype. They
will also be used to test the hypothesis that over-expression of suPAR in mice
on a type I diabetic background potentiates the renal phenotype associated with
these diabetic mouse models. These mouse lines will be made available to the
interested investigative community as soon as validation is complete.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 41224
Supply Total Costs 5000
Equipment Total Costs 0
Travel/Other Total Costs 16276
Direct Costs 62500
Indirect Costs Proposed 37500
Total Costs Proposed 100000
Total Costs Approved 100000
Start Date 10/1/2012
End Date 9/30/2014
IFO Name Garrison, Kim
IFO E-Mail Address pennaors@lists.upenn.edu
IACUC/IRB No. 99999
IACUC/IRB Institution University of Pennsylvania
Entity ID No. 1231352685A1
Report Request Date 10/30/2014
T1D NO
TypeCount
Invoices 16
Progress Reports 2
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  12GHSU20325034-20University of Pennsylvania9/24/2013$3,528.79$2,117.27$5,646.06-View PDF
  View  12GHSU20325034-20University of Pennsylvania8/19/2014$1,265.70-$1,265.70-View PDF
  View  12GHSU20325034-20University of Pennsylvania8/12/2013$2,186.75$1,312.05$3,498.80-View PDF
  View  12GHSU20325034-20University of Pennsylvania7/20/2013$4,030.21$2,418.13$6,448.34-View PDF
  View  12GHSU20325034-20University of Pennsylvania6/5/2013$2,715.75$1,629.45$4,345.20-View PDF
  View  12GHSU20325034-20University of Pennsylvania6/12/2014$7,102.96-$7,102.96-View PDF
  View  12GHSU20325034-20University of Pennsylvania5/7/2013$2,787.49$1,672.49$4,459.98-View PDF
  View  12GHSU20325034-20University of Pennsylvania4/4/2014$4,381.00-$4,381.00-View PDF
  View  12GHSU20325034-20University of Pennsylvania4/4/2013$2,068.44$1,241.06$3,309.50-View PDF
  View  12GHSU20325034-20University of Pennsylvania3/8/2013$10,089.30$6,053.58$16,142.88-View PDF
  View  12GHSU20325034-20University of Pennsylvania3/7/2014$3,916.16$2,349.69$6,265.85-View PDF
  View  12GHSU20325034-20University of Pennsylvania2/6/2014$3,479.15$2,087.49$5,566.64-View PDF
  View  12GHSU20325034-20University of Pennsylvania12/4/2013$3,419.03$2,051.42$5,470.45-View PDF
  View  12GHSU20325034-20University of Pennsylvania11/12/2013$9,272.87$5,563.72$14,836.59-View PDF
  View  12GHSU20325034-20University of Pennsylvania10/7/2013$3,677.53$2,206.52$5,884.05-View PDF
  View  12GHSU20325034-20University of Pennsylvania1/8/2014$3,360.00$2,016.00$5,376.00-View PDF
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