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An outbred mouse strain to study diabetic nephropathy
Summary Data Summary
Applicant Harris, Raymond
E-Mail Address ray.harris@vanderbilt.edu
Project Title An outbred mouse strain to study diabetic nephropathy
CBU ID 10MCG105
External SubContract ID 20497-18
Diabetic Complication Nephropathy
Funding Program Group Pilot & Feasibility [PF2008]
Abstract To date, the AMDCC has nearly exclusively characterized inbred laboratory mice
strains to study the development diabetes nephropathy. These studies support the
influence of genetic risk factors as contributing to diabetic nephropathy in
these inbred lines. In this regard some strains, like DBA2 develop more robust
nephropathy than C57BL/6. Nevertheless, the complexity the genomes of inbred
mouse strain are drastically reduced, as compared to the genetic complexity of
outbred human populations. Inbred mice are homozygous at all loci; whereas in
outbred populations, loci allowed to exist in both heterozygous and homozygous
states . Furthermore during the process of brother-sister mating used to derive
inbred mouse strains, any polymorphisms that either decrease fecundity or are
lethal when homozygous, are lost. If similar mutations contribute, in a dominant
or semi-dominant fashion, to human diabetic nephropathy, this variability would
never be seen in inbred mouse models. In this regard, one of the specific
suggestions of the AMDCC External Scientific Committee was to consider utilizing
outbred mouse strains to investigate genetic predisposition for development of
diabetic complications.
We propose to characterize the progression of nephropathy in diabetic outbred
CD-1 mice. A recent study has reported that CD-1 mice develop significant
nephropathy in a streptozotocin-induced model of diabetes. This study reported
that mice made diabetic by a high dose (single injection) streptozotocin
protocol develop ESRD associated with prominent tubulointerstitial nephritis and
fibrosis within 3 months and die because of diabetic complications by 6-7
months. In this regard, our own preliminary data in CD-1 mice indicate
significant diversity in the levels of albuminuria (following STZ induced
diabetes) among individual mice (see below). Such heterogeneity may indicate
that outbred mice might more closely resemble the heterogeneity of human
populations and might also provide the opportunity to capture dominant genes
that contribute to increased albuminuria and diabetic nephropathy. For this
reason, we propose to characterize the extent and heterogeneity of diabetic
nephropathy in CD-1 mice and to begin to develop crosses for detecting dominant
heritable traits predisposing to development and/or progression of diabetic
nephropathy. Our first specific aim will be to characterize the variability of
the development of nephropathy in the CD-1 strain. Our second specific aim is to
to initiate a backcross of CD-1 mice with B6Akita mice, a strain resistant to
development of diabetic nephropathy, in order to begin to identify potential
dominant alleles that contribute to diabetic nephropathy.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 30963
Supply Total Costs 17375
Equipment Total Costs 0
Travel/Other Total Costs 17300
Direct Costs 65638
Indirect Costs Proposed 6564
Total Costs Proposed 72202
Total Costs Approved 72202
Start Date 8/1/2008
End Date 7/31/2009
IFO Name Salberg, Libby
IFO E-Mail Address vumc.reserach.grants@vanderbilt.edu
IACUC/IRB No. A3227-01
IACUC/IRB Institution Vanderbilt University
Entity ID No.
Report Request Date 9/28/2009
T1D NO
TypeCount
Invoices 1
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  10MCG10520497-18Vanderbilt University11/28/2012$19,648.13$11,788.87$31,437.00$40,765.00View PDF


Reports
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