Effect of Serum Response Factor (SRF) gene deletion on the adult cardiac gene expression at baseline and in response to phenylephrine

The objective of this study is to assess the effects of the Serum Response Factor deletion on the cardiac gene expression program at different time points after the deletion (day 8 and day 25) and to compare the response of SRF-deficient heart and control heart to phenylephrine, an alpha-adrenergic agonist triggering cardiac hypertrophy. To generate cardiomyocyte-specific SRF knockout, 10 week-old mice homozygous for the [SRF-flex2neo] allele bearing one copy of the [alphaMHC-MerCreMer] transgene (SRFHKO mice) (Reference 1) were injected i.p. with 0.7mg of tamoxifen for 3 days. All control (SRF-flex2neo littermates) and SRFHKO mice were systematically injected with tamoxifen to normalize for any effects due to tamoxifen. For the mice treated with phenylephrine (PE), the drug was administrated at 80 mg/kg/day from day 10 to day 25 after the first day of tamoxifen injection, using Alzet osmotic minipumps. Reference: Temporally controlled onset of dilated cardiomyopathy through disruption of the SRF gene in adult heart. Parlakian A, Charvet C, Escoubet B, Mericskay M, Molkentin JD, Gary-Bobo G, De Windt LJ, Ludosky MA, Paulin D, Daegelen D, Tuil D, Li Z. Circulation. 2005 Nov 8;112(19):2930-9. PMID: 16260633