Sign-up for our newsletter
MAIN
Event Calendar
Awardee Reports
ABOUT DIACOMP
Citing DiaComp
Contact
Committees
Institutions
Awardee Reports
Publications
Bioinformatics
RESOURCES
Protocols & Methods
Reagents & Resources
Mouse Diet
Breeding Schemes
Validation Criteria
IMPC / KOMP Data
Publications
Bioinformatics
CONTACT
PARTICIPANT AREA
Login
▹
Publications
▹
Home
Publication
A Novel Type 2 Diabetes Mouse Model of Combined Diabetic Kidney Disease and
Atherosclerosis.
Authors
Bornfeldt KE, Kramer F, Batorsky A, Choi J, Hudkins KL, Tontonoz P, Alpers CE,
Kanter JE
Submitted By
Charles Alpers on 2/19/2018
Status
Published
Journal
The American journal of pathology
Year
2018
Date Published
2/1/2018
Volume : Pages
188 : 343 - 352
PubMed Reference
29154962
Abstract
Diabetic kidney disease and atherosclerotic disease are major causes of
morbidity and mortality associated with type 2 diabetes (T2D), and diabetic
kidney disease is a major cardiovascular risk factor. The black and tan,
brachyury (BTBR) mouse strain with leptin deficiency (Lepob) has emerged as one
of the best models of human diabetic kidney disease. However, no T2D mouse model
of combined diabetic kidney disease and atherosclerosis exists. Our goal was to
generate such a model. To this end, the low-density lipoprotein (LDL) receptor
was targeted for degradation via inducible degrader of the LDL receptor (IDOL)
overexpression, using liver-targeted adenoassociated virus serotype DJ/8
(AAV-DJ/8) in BTBR wild-type and BTBR Lepobmice. Liver-targeted IDOL-AAV-DJ/8
increased plasma LDL cholesterol compared with the control enhanced green
fluorescent protein AAV-DJ/8. IDOL-induced dyslipidemia caused formation of
atherosclerotic lesions of an intermediate stage, which contained both
macrophages and smooth muscle cells. BTBR Lepobmice exhibited diabetic kidney
disease. IDOL-induced dyslipidemia worsened albuminuria and glomerular
macrophage accumulation but had no effect on mesangial expansion or podocyte
numbers. Thus, by inducing hepatic degradation of the LDL receptor, we generated
a T2D model of combined kidney disease and atherosclerosis. This model provides
a new tool to study mechanisms, interactions, and treatment strategies of kidney
disease and atherosclerosis in T2D.
Complications
All Complications
Bioinformatics
Bone
Cardiomyopathy
Cardiovascular
Gastro-Intestinal (GI)
Nephropathy
Neuropathy & Neurocognition
Pediatric Endocrinology
Retinopathy
Uropathy
Wound Healing
Welcome to the DiaComp Login / Account Request Page.
Email Address:
Password:
Note: Passwords are case-sensitive.
Please save my Email Address on this machine.
Not a member?
If you are a funded DiaComp investigator, a member of an investigator's lab,
or an External Scientific Panel member to the consortium, please
request an account.
Forgot your password?
Enter your Email Address and
click here.
ERROR!
There was a problem with the page:
User Info
User Confirm
Please acknowledge all posters, manuscripts or scientific materials that were generated in part or whole using funds from the Diabetic Complications Consortium(DiaComp) using the following text:
Financial support for this work provided by the NIDDK Diabetic Complications Consortium (RRID:SCR_001415, www.diacomp.org), grants DK076169 and DK115255
Citation text and image have been copied to your clipboard. You may now paste them into your document. Thank you!