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Diabetic Complications in Germ-Free BTBR and BTBRob/ob mice
Summary Data Summary
Applicant Smith, Kelly
E-Mail Address kelsmith@uw.edu
Project Title Diabetic Complications in Germ-Free BTBR and BTBRob/ob mice
CBU ID 14GHSU1402
External SubContract ID 25034-52
Diabetic Complication Nephropathy
Funding Program Group Pilot & Feasibility [PF2014]
Abstract Obesity and metabolic syndrome are leading causes of type II diabetes, which is
a growing epidemic and one of the major global health problems that we face in
the 21st century. Obesity and diabetes are associated with an altered gut
microbiota that further aggravates metabolic syndrome, and may promote
inflammation and contribute to diabetic complications. The focus of this grant
application is the role of the microbiome in modulating complications of
diabetes. My collaborator, Charles Alpers (University of Washington), has
recently characterized a new mouse model of type II diabetes, which develops
several diabetic complications, notably diabetic nephropathy, as well as
cardiomyopathy and retinopathy. BTBR WT mice develop pre-diabetes. When made
leptin deficient, The BTBRob/ob mouse develops progressive obesity and type II
diabetes. The novel aspect of this mouse model of type II diabetes is that these
mice also develop clinical and morphologic features that closely mimic diabetic
nephropathy in humans. Thus this model provides a tool to dissect factors that
contribute not only to the development of insulin resistance and diabetes, but
also end organ damage and specifically, diabetic nephropathy. To test whether
the gut microbiome contributes to disease progression in these mice, we treated
BTBR WT and ob/ob mice with broad spectrum antibiotics between 4-16 weeks of
life. Antiobiotic treatment resulted in a significant improvement in
pre-diabetes in WT mice, but paradoxical increased mortality and no improvement
in severe diabetes in the ob/ob mice. Fialure to completely suppress gut
microbes in the ob/ob mice was a complicating factor. We hypothesize that end
organ complications from genetic obesity and diabetes will be improved by
definitively eliminating the microbiome through the generation of germ-free
mice. We will test our hypothesis with the following specific Aims: 1) To
develop a GF model of pre-diabetes and diabetes in the BTBR and BTBRob/ob mice,
and 2) To compare the development of pre-diabetes and diabetes in GF and
conventional BTBR and BTBRob/ob mice.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 45887
Supply Total Costs 10500
Equipment Total Costs 0
Travel/Other Total Costs 34522
Direct Costs 90909
Indirect Costs Proposed 9091
Total Costs Proposed 100000
Total Costs Approved 100000
Start Date 10/1/2014
End Date 9/30/2015
IFO Name DeFries, Kirsten
IFO E-Mail Address gcahelp@uw.edu
IACUC/IRB No. 4031-01
IACUC/IRB Institution University of Washington
Entity ID No. 91-6001537
Report Request Date 1/1/3000
T1D NO
TypeCount
Invoices 17
Progress Reports 0
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  14GHSU140225034-52University of Washington9/10/2015$7,927.84-$7,927.84-View PDF
  View  14GHSU140225034-52University of Washington8/11/2015$5,996.70-$5,996.70-View PDF
  View  14GHSU140225034-52University of Washington7/9/2015$7,299.87-$7,299.87-View PDF
  View  14GHSU140225034-52University of Washington6/11/2015$3,829.32-$3,829.32-View PDF
  View  14GHSU140225034-52University of Washington5/8/2015$4,089.74-$4,089.74-View PDF
  View  14GHSU140225034-52University of Washington5/25/2016$995.29$99.54$1,094.83-View PDF
  View  14GHSU140225034-52University of Washington4/11/2016$4,914.51$491.48$5,405.99-View PDF
  View  14GHSU140225034-52University of Washington4/10/2015$4,298.47-$4,298.47-View PDF
  View  14GHSU140225034-52University of Washington3/9/2016$9,509.81-$9,509.81-View PDF
  View  14GHSU140225034-52University of Washington3/10/2015$2,386.35-$2,386.35-View PDF
  View  14GHSU140225034-52University of Washington2/10/2016$7,156.42-$7,156.42-View PDF
  View  14GHSU140225034-52University of Washington2/10/2015$2,879.42-$2,879.42-View PDF
  View  14GHSU140225034-52University of Washington12/9/2015$10,270.40-$10,270.40-View PDF
  View  14GHSU140225034-52University of Washington11/12/2015$7,444.28$744.43$8,188.71-View PDF
  View  14GHSU140225034-52University of Washington10/9/2015$8,433.57-$8,433.57-View PDF
  View  14GHSU140225034-52University of Washington1/9/2015$3,186.35-$3,186.35-View PDF
  View  14GHSU140225034-52University of Washington1/15/2016$8,046.21-$8,046.21-View PDF
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