Matthew Breyer

Personal Information
Title Professor
Expertise Nephropathy
Institution Eli Lilly and Company
Data Summary
TypeCount
Grants/SubContracts 1
Progress Reports 3
Presentations 3
Publications 22
Protocols 0
Committees 2
Experiments 0
Strains 14
Models 1

Generating Mouse Mutants with Diabetic Nephropathy
Grant Number: 1U01DK061018-01

Abstract: Diabetic nephropathy (DN) is a disease of monumental proportions both in terms of human suffering and public health expenditures. Approximately six percent of the U.S. population has diabetes mellitus, 10-20% of which develop DN, ultimately progressing to end stage renal disease (ESRD). The factors contributing to DN remain obscure. While hyperglycemia is a necessary trigger, alone, it is insufficient to cause DN. Sibling studies suggest a strong genetic component, however defining the specific genetic loci contributing to DN in man has been confounded by the heterogeneous causes of diabetes, and by the diversity of human genetic background. In contrast, the wide availability of genetically homogenous mouse strains, coupled with advances in transgenic technology, make mice uniquely amenable to dissection of the molecular mechanisms of disease. As in man, most mice do not develop diabetic nephropathy, and the array of genes that confer susceptibility to DN to this minority, have not been characterized. This proposal is to generate a robust murine model of DN that closely parallels the human disease; that is genetically defined; and can be easily transferred between mouse strains. To achieve these goals we propose to identify specific genes that convert the "nephropathy resistant" C57BL/6 strain to one that develops DN. We will take two approaches. The first will use a "candidate gene" approach. In man, patients susceptible to DN exhibit worse hypertension and dyslipidemia than those resistant to nephropathy. Treatment of these conditions slows the progression of nephropathy. Polymorphisms in Angiotensinogen (Atg) eNOS and ApoE alleles have been described in susceptible patients. The first specific aim will examine the effect of superimposing the hypertensive human Atg transgenic, eNOS-/- or hyperlipidemic ApoE-/- alleles on two different models of diabetes, insulin deficient HN6 transgenic mice and insulin resistant db/db mice. The second approach will attempt to identify novel dominant modifiers that predispose to DN. Diabetic HNF6 or db/db C57BL/6 mice will be mutagenized with ethylnitrosourea (ENU) and G 1 offspring screened for DN (renal insufficiency and/or proteinuria). These studies should not only yield a well-defined mouse model of DN, but also provide important new information regarding genes that contribute to the development of DN.


Institution: Eli Lilly and Company
550 University Blvd
Indianapolis, IN
Fiscal Year:2001
Department:
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Progress Reports

No funding program application progress reports found.

Annual Reports

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Breyer, Matthew (2004)
2004Annual Report
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Breyer, Matthew (2005)
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Breyer, Matthew (2006)
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 PublicationAltmetricsSubmitted ByPubMed IDStatus

Year: 2013; Items: 1

 
Diabetic Nephropathy: A National Dialogue.
Breyer MD, Coffman TM, Flessner MF, Fried LF, Harris RC, Ketchum CJ, Kretzler M, Nelson RG, Sedor JR, Susztak K, on behalf of the Kidney Research National Dialogue (KRND)
Clinical journal of the American Society of Nephrology : CJASN, 2013
23788618
Published

Year: 2012; Items: 3

 
Generation of a conditional allele for the mouse endothelial nitric oxide synthase gene.
Jiang R, Wang S, Takahashi K, Fujita H, Fruci CR, Breyer MD, Harris RC, Takahashi T
Genesis (New York, N.Y. : 2000), 2012 (50), 685 - 692
22467476
Published
 
SOD1, but not SOD3, deficiency accelerates diabetic renal injury in C57BL/6-Ins2(Akita) diabetic mice.
Fujita H, Fujishima H, Takahashi K, Sato T, Shimizu T, Morii T, Shimizu T, Shirasawa T, Qi Z, Breyer MD, Harris RC, Yamada Y, Takahashi T
Metabolism: clinical and experimental, 2012 (61), 1714 - 1724
22632894
Published
 
Drug discovery for diabetic nephropathy: trying the leap from mouse to man.
Breyer MD
Seminars in nephrology, 2012 (32), 445 - 451
23062985
Published

Year: 2009; Items: 2

 
Reduction of renal superoxide dismutase in progressive diabetic nephropathy.
Fujita H, Fujishima H, Chida S, Takahashi K, Qi Z, Kanetsuna Y, Breyer MD, Harris RC, Yamada Y, Takahashi T
Journal of the American Society of Nephrology : JASN, 2009 (20(6)), 1303 - 1313
19470681
Published
 
Mouse Models of Diabetic Nephropathy: A Midstream Analysis from the Diabetic Complications Consortium
Frank C. Brosius IIIa, Charles E. Alpersb, Erwin P. Bottingerc, Matthew D. Breyerd, ThomasM. Coffmane, Susan B. Gurleye, Raymond C. Harrisf, Masao Kakokig, Matthias Kretzler, Edward H. Leiterh, Moshe Levii, Richard A. McIndoej, Kumar Sharmak, Oliver Smithiesg, Katalin Susztakl, Nobuyuki Takahashig, Takamune Takahashif
Journal of the American Society of Nephrology : JASN, 2009 (20(12)), 2503 - 2512
19729434
Published

Year: 2008; Items: 2

 
Insight into the genetics of diabetic nephropathy through the study of mice.
Breyer MD, Qi Z, Tchekneva EE, Harris RC
Current opinion in nephrology and hypertension, 2008 (17(1)), 82 - 86
18090675
Published
 
Single amino acid substitution in aquaporin 11 causes renal failure.
Tchekneva EE, Khuchua Z, Davis LS, Kadkina V, Dunn SR, Bachman S, Ishibashi K, Rinchik EM, Harris RC, Dikov MM, Breyer MD
Journal of the American Society of Nephrology : JASN, 2008 (19(10)), 1955 - 1964
18701606
Published

Year: 2007; Items: 4

 
A sensitized screen of N-ethyl-N-nitrosourea-mutagenized mice identifies dominant mutants predisposed to diabetic nephropathy.
Tchekneva EE, Rinchik EM, Polosukhina D, Davis LS, Kadkina V, Mohamed Y, Dunn SR, Sharma K, Qi Z, Fogo AB, Breyer MD
Journal of the American Society of Nephrology : JASN, 2007 (18), 103 - 112
17151334
Published
 
Genetics of diabetic nephropathy: lessons from mice.
Breyer MD, Tchekneva E, Qi Z, Takahashi T, Fogo AB, Zhao HJ, Harris RC
Seminars in nephrology, 2007 (27)
17418691
Published
 
Deficiency of endothelial nitric-oxide synthase confers susceptibility to diabetic nephropathy in nephropathy-resistant inbred mice.
Kanetsuna Y, Takahashi K, Nagata M, Gannon MA, Breyer MD, Harris RC, Takahashi T
The American journal of pathology, 2007 (170), 1473 - 1484
17456755
Published
 
Examining diabetic nephropathy through the lens of mouse genetics.
Breyer MD, Tchekneva E, Qi Z, Takahashi T, Fogo AB, Harris RC
Current diabetes reports, 2007 (7(6)), 459 - 466
18255011
Published

Year: 2006; Items: 5

 
Accelerated Diabetic Nephropathy in Mice Lacking the Peroxisome Proliferator-Activated Receptor-alpha
Cheol Whee Park, M.D., Hyeong Wook Kim, M.D., Seung Hyun Ko, M.D., Hyun Wha Chung, M.D., Sun Woo Lim, Ph.D., Chul Woo Yang, M.D., Yoon Sik Chang, M.D., Akira Sugawara, M.D., YouFei Guan, M.D., Matthew D. Breyer
Diabetes, 2006 (55), 885 - 893
16567507
Published
 
Diabetic nephropathy: leveraging mouse genetics.
Breyer MD, Qi Z, Tchekneva E
Current opinion in nephrology and hypertension, 2006 (15(3)), 227 - 232
16609287
Published
 
Characterization of Diabetic Nephropathy in a Transgenic Model of Nonobese Diabetes
Yukiko Kanetsuna, Keita Hirano, Michio Nagata, Maureen A Gannon, Raymond C. Harris, Matthew D. Breyer, and Takamune Takahashi
American journal of physiology. Renal physiology, 2006 (291(6)), F1315 - F1322
16705146
Published
 
Glomerular injury is exacerbated in diabetic integrin alpha1-null mice.
Zent R, Yan X, Su Y, Hudson BG, Borza DB, Moeckel GW, Qi Z, Sado Y, Breyer MD, Voziyan P, Pozzi A
Kidney international, 2006 (70)
16775606
Published
 
Endothelial Nitric Oxide Synthase Deficiency Produces Accelerated Nephropathy in Diabetic Mice
Hui John Zhao, Suwan Wang, Huifang Cheng, Ming-zhi Zhang, Takamune Takahashi, Agnes B. Fogo, Matthew D. Breyer, and Raymond C. Harris
Journal of the American Society of Nephrology : JASN, 2006 (17), 2664 - 2669
16971655
Published

Year: 2005; Items: 4

 
Mouse Models of Diabetic Nephropathy
MATTHEW D. BREYER, ERWIN BÖTTINGER, FRANK C. BROSIUS, III, THOMAS M. COFFMAN, RAYMOND C. HARRIS, CHARLES W. HEILIG, AND KUMAR SHARMA (FOR THE AMDCC)
Journal of the American Society of Nephrology : JASN, 2005 (16), 27 - 45
15563560
Published
 
Diabetic nephropathy: of mice and men.
Breyer MD, Böttinger E, Brosius FC, Coffman TM, Fogo A, Harris RC, Heilig CW, Sharma K
Advances in chronic kidney disease, 2005 (12(2)), 128 - 145
15822049
Published
 
Expression of mediators of renal injury in the remnant kidney of ROP mice is attenuated by cyclooxygenase-2 inhibition.
Cheng H, Zhang M, Moeckel GW, Zhao Y, Wang S, Qi Z, Breyer MD, Harris RC
Nephron. Experimental nephrology, 2005 (101), e75 - 85
15995341
Published
 
Characterization of susceptibility of inbred mouse strains to diabetic nephropathy.
Qi Z, Fujita H, Jin J, Davis LS, Wang Y, Fogo AB, Breyer MD
Diabetes, 2005 (54), 2628 - 2637
16123351
Published

Year: 2004; Items: 1

 
Serial Determination of Glomerular Filtration Rate in Conscious Mice Using FITC-Inulin Clearance
Zhonghua Qi, Irene Whitt, Amit Mehta, Jianping Jin, Min Zhao, Raymond C. Harris, Agnes B. Fogo, Matthew D. Breyer
American journal of physiology. Renal physiology, 2004 (286), F590 - F596
14600035
Published

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No protocols found.

No experiments found.