Cardiac hypertrophy and sudden death in mice with a genetically renin transgene

Kathleen M.I. Caron, Leighton R. James, Hyung Suk Kim, Josh Knowles, Rick Uhlir, Lan Mao, John R. Hagaman, Wayne Cascio, Howard Rockman, Oliver Smithies

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Abstract

Several mouse models have already proved valuable for investigating hypertrophic responses to cardiac stress. Here, we characterize one caused by a well defined single copy transgene, RenTgMK, that genetically clamps plasma renin and thence angiotensin II at high levels. All of the transgenic males develop concentric cardiac hypertrophy with fibrosis but without dilatation. Over half die suddenly aged 6-8 months. Telemetry showed disturbances in diurnal rhythms a few days before death and, later, electrocardiographic disturbances comparable to those in humans with congestive heart failure. Expression of seven hypertrophy-related genes in this and two categorically different models (lack of atrial natriuretic peptide receptor A; overexpression of calsequestrin) were compared. Statistical analyses show that ventricular expressions of the genes coding for atrial natriuretic peptide, β myosin heavy chain, medium chain acyl-CoA dehydrogenase, and adrenomedullin correlate equally well with the degree of hypertrophy, although their ranges of expression are, respectively, 50-, 30-, 10-, and 3-fold.

Original languageEnglish (US)
Pages (from-to)3106-3111
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number9
DOIs
StatePublished - Mar 2 2004

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Cardiomegaly
Sudden Death
Transgenes
Renin
Hypertrophy
Calsequestrin
Atrial Natriuretic Factor Receptors
Acyl-CoA Dehydrogenase
Adrenomedullin
Telemetry
Myosin Heavy Chains
Atrial Natriuretic Factor
Circadian Rhythm
Angiotensin II
Dilatation
Fibrosis
Heart Failure
Gene Expression
Genes
atrial natriuretic factor receptor A

ASJC Scopus subject areas

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Cardiac hypertrophy and sudden death in mice with a genetically renin transgene. / Caron, Kathleen M.I.; James, Leighton R.; Kim, Hyung Suk; Knowles, Josh; Uhlir, Rick; Mao, Lan; Hagaman, John R.; Cascio, Wayne; Rockman, Howard; Smithies, Oliver.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 9, 02.03.2004, p. 3106-3111.

Research output: Contribution to journalArticle

Caron, KMI, James, LR, Kim, HS, Knowles, J, Uhlir, R, Mao, L, Hagaman, JR, Cascio, W, Rockman, H & Smithies, O 2004, 'Cardiac hypertrophy and sudden death in mice with a genetically renin transgene', Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 9, pp. 3106-3111. https://doi.org/10.1073/pnas.0307333101
Caron, Kathleen M.I. ; James, Leighton R. ; Kim, Hyung Suk ; Knowles, Josh ; Uhlir, Rick ; Mao, Lan ; Hagaman, John R. ; Cascio, Wayne ; Rockman, Howard ; Smithies, Oliver. / Cardiac hypertrophy and sudden death in mice with a genetically renin transgene. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 9. pp. 3106-3111.
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