Publication

Analysis of Cre-mediated genetic deletion of Gdf11 in cardiomyocytes of young mice

Garbern, J., Kristl, A. C., Bassaneze, V., Vujic, A., Schoemaker, H., Sereda, R., Peng, L., Ricci-Blair, E. M., Goldstein, J. M., Walker, R. G., Bhasin, S., Wagers, A. J. & Lee, R. T., 24-May-2019, In : American Journal of Physiology - Heart and Circulatory Physiology. 39 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Garbern, J., Kristl, A. C., Bassaneze, V., Vujic, A., Schoemaker, H., Sereda, R., ... Lee, R. T. (2019). Analysis of Cre-mediated genetic deletion of Gdf11 in cardiomyocytes of young mice. American Journal of Physiology - Heart and Circulatory Physiology. https://doi.org/10.1152/ajpheart.00615.2018

Author

Garbern, Jessica ; Kristl, Amy C ; Bassaneze, Vinicius ; Vujic, Ana ; Schoemaker, Henk ; Sereda, Rebecca ; Peng, Liming ; Ricci-Blair, Elisabeth M ; Goldstein, Jill M ; Walker, Ryan G ; Bhasin, Shalender ; Wagers, Amy J ; Lee, Richard T. / Analysis of Cre-mediated genetic deletion of Gdf11 in cardiomyocytes of young mice. In: American Journal of Physiology - Heart and Circulatory Physiology. 2019.

Harvard

Garbern, J, Kristl, AC, Bassaneze, V, Vujic, A, Schoemaker, H, Sereda, R, Peng, L, Ricci-Blair, EM, Goldstein, JM, Walker, RG, Bhasin, S, Wagers, AJ & Lee, RT 2019, 'Analysis of Cre-mediated genetic deletion of Gdf11 in cardiomyocytes of young mice', American Journal of Physiology - Heart and Circulatory Physiology. https://doi.org/10.1152/ajpheart.00615.2018

Standard

Analysis of Cre-mediated genetic deletion of Gdf11 in cardiomyocytes of young mice. / Garbern, Jessica; Kristl, Amy C; Bassaneze, Vinicius; Vujic, Ana; Schoemaker, Henk; Sereda, Rebecca; Peng, Liming; Ricci-Blair, Elisabeth M; Goldstein, Jill M; Walker, Ryan G; Bhasin, Shalender; Wagers, Amy J; Lee, Richard T.

In: American Journal of Physiology - Heart and Circulatory Physiology, 24.05.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Garbern J, Kristl AC, Bassaneze V, Vujic A, Schoemaker H, Sereda R et al. Analysis of Cre-mediated genetic deletion of Gdf11 in cardiomyocytes of young mice. American Journal of Physiology - Heart and Circulatory Physiology. 2019 May 24. https://doi.org/10.1152/ajpheart.00615.2018


BibTeX

@article{7c3a605e83164e39837af41529eb0a92,
title = "Analysis of Cre-mediated genetic deletion of Gdf11 in cardiomyocytes of young mice",
abstract = "Administration of active growth differentiation factor 11 (GDF11) to aged mice can reduce cardiac hypertrophy, and low serum levels of GDF11 measured together with the related protein, myostatin (also known as GDF8), predict future morbidity and mortality in coronary heart patients. Using mice with a loxP-flanked ({"}floxed{"}) allele of Gdf11 and Myh6-driven expression of Cre recombinase to delete Gdf11 in cardiomyocytes, we tested the hypothesis that cardiac-specific Gdf11 deficiency might lead to cardiac hypertrophy in young adulthood. We observed that targeted deletion of Gdf11 in cardiomyocytes does not cause cardiac hypertrophy but rather leads to left ventricular dilation when compared to control mice carrying only the Myh6-cre or Gdf11-floxed alleles, suggesting a possible etiology for dilated cardiomyopathy. However, the mechanism underlying this finding remains unclear due to multiple confounding effects associated with the selected model. First, whole heart Gdf11 expression did not decrease in Myh6-cre;Gdf11-floxed mice, possibly due to upregulation of Gdf11 in non-cardiomyocytes in the heart. Second, we observed Cre-associated toxicity, with lower body weights and increased global fibrosis in Cre-only control male mice compared to flox-only controls, making it challenging to infer which changes in Myh6-cre;Gdf11-floxed mice were due to Cre toxicity versus deletion of Gdf11. Third, we observed differential expression of cre mRNA in Cre-only controls compared to the cardiomyocyte-specific knockout mice, also making comparison between these two groups difficult. Thus, targeted Gdf11 deletion in cardiomyocytes may lead to left ventricular dilation without hypertrophy, but alternative animal models are necessary to understand the mechanism for these findings.",
author = "Jessica Garbern and Kristl, {Amy C} and Vinicius Bassaneze and Ana Vujic and Henk Schoemaker and Rebecca Sereda and Liming Peng and Ricci-Blair, {Elisabeth M} and Goldstein, {Jill M} and Walker, {Ryan G} and Shalender Bhasin and Wagers, {Amy J} and Lee, {Richard T}",
year = "2019",
month = "5",
day = "24",
doi = "10.1152/ajpheart.00615.2018",
language = "English",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "1522-1539",
publisher = "AMER PHYSIOLOGICAL SOC",

}

RIS

TY - JOUR

T1 - Analysis of Cre-mediated genetic deletion of Gdf11 in cardiomyocytes of young mice

AU - Garbern, Jessica

AU - Kristl, Amy C

AU - Bassaneze, Vinicius

AU - Vujic, Ana

AU - Schoemaker, Henk

AU - Sereda, Rebecca

AU - Peng, Liming

AU - Ricci-Blair, Elisabeth M

AU - Goldstein, Jill M

AU - Walker, Ryan G

AU - Bhasin, Shalender

AU - Wagers, Amy J

AU - Lee, Richard T

PY - 2019/5/24

Y1 - 2019/5/24

N2 - Administration of active growth differentiation factor 11 (GDF11) to aged mice can reduce cardiac hypertrophy, and low serum levels of GDF11 measured together with the related protein, myostatin (also known as GDF8), predict future morbidity and mortality in coronary heart patients. Using mice with a loxP-flanked ("floxed") allele of Gdf11 and Myh6-driven expression of Cre recombinase to delete Gdf11 in cardiomyocytes, we tested the hypothesis that cardiac-specific Gdf11 deficiency might lead to cardiac hypertrophy in young adulthood. We observed that targeted deletion of Gdf11 in cardiomyocytes does not cause cardiac hypertrophy but rather leads to left ventricular dilation when compared to control mice carrying only the Myh6-cre or Gdf11-floxed alleles, suggesting a possible etiology for dilated cardiomyopathy. However, the mechanism underlying this finding remains unclear due to multiple confounding effects associated with the selected model. First, whole heart Gdf11 expression did not decrease in Myh6-cre;Gdf11-floxed mice, possibly due to upregulation of Gdf11 in non-cardiomyocytes in the heart. Second, we observed Cre-associated toxicity, with lower body weights and increased global fibrosis in Cre-only control male mice compared to flox-only controls, making it challenging to infer which changes in Myh6-cre;Gdf11-floxed mice were due to Cre toxicity versus deletion of Gdf11. Third, we observed differential expression of cre mRNA in Cre-only controls compared to the cardiomyocyte-specific knockout mice, also making comparison between these two groups difficult. Thus, targeted Gdf11 deletion in cardiomyocytes may lead to left ventricular dilation without hypertrophy, but alternative animal models are necessary to understand the mechanism for these findings.

AB - Administration of active growth differentiation factor 11 (GDF11) to aged mice can reduce cardiac hypertrophy, and low serum levels of GDF11 measured together with the related protein, myostatin (also known as GDF8), predict future morbidity and mortality in coronary heart patients. Using mice with a loxP-flanked ("floxed") allele of Gdf11 and Myh6-driven expression of Cre recombinase to delete Gdf11 in cardiomyocytes, we tested the hypothesis that cardiac-specific Gdf11 deficiency might lead to cardiac hypertrophy in young adulthood. We observed that targeted deletion of Gdf11 in cardiomyocytes does not cause cardiac hypertrophy but rather leads to left ventricular dilation when compared to control mice carrying only the Myh6-cre or Gdf11-floxed alleles, suggesting a possible etiology for dilated cardiomyopathy. However, the mechanism underlying this finding remains unclear due to multiple confounding effects associated with the selected model. First, whole heart Gdf11 expression did not decrease in Myh6-cre;Gdf11-floxed mice, possibly due to upregulation of Gdf11 in non-cardiomyocytes in the heart. Second, we observed Cre-associated toxicity, with lower body weights and increased global fibrosis in Cre-only control male mice compared to flox-only controls, making it challenging to infer which changes in Myh6-cre;Gdf11-floxed mice were due to Cre toxicity versus deletion of Gdf11. Third, we observed differential expression of cre mRNA in Cre-only controls compared to the cardiomyocyte-specific knockout mice, also making comparison between these two groups difficult. Thus, targeted Gdf11 deletion in cardiomyocytes may lead to left ventricular dilation without hypertrophy, but alternative animal models are necessary to understand the mechanism for these findings.

U2 - 10.1152/ajpheart.00615.2018

DO - 10.1152/ajpheart.00615.2018

M3 - Article

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 1522-1539

ER -

ID: 84988692