Background

Benchmark data set for cardiac development, maturation, and aging

We are interested in identifying the complex regulatory mechanisms underlying cardiac development from embryonic stages through adolescence and adulthood. Many of our knockout mouse models for congenital heart disease die during embryonic development, whereas other heart failure models survive into adulthood.

Therefore, we created benchmark sets of expression profiles at different developmental stages to monitor changes in cardiac gene expression over time. Most of our transgenic and experimental models of cardiac hypertrophy and heart failure are generated in an FVB strain genetic background. Since the benchmark data set will serve as a reference for comparisons with these models, we used the same genetic background and chose time points to match the onset, progression, and late stage of cardiac diseases in our models.

Gene expression during embryonic cardiac development

Within this data set, we generated the embryonic expression profile at one developmental stage and one early neonatal stage. This gives us a general overview of the pre- and postnatal gene expression profile. However, cardiac development is a complex process involving the concerted action of many regulatory factors at each developmental stage. Therefore, a separate more detailed benchmark set of normal cardiac development will be created in C57BL6 mice, covering gene expression changes in daily intervals throughout embryonic development.

Gene expression related to aging

In addition to monitoring changes related to cardiac development, this data set also captures changes in gene expression that are related to the aging of the heart. Independent of disease, age-associated changes in cardiovascular function include anatomical, physiological, and haemodynamic alterations. Diminished responsiveness to neurohumoral stimuli, increased arterial “stiffness”, impaired left ventricular filling due to changes in relaxation and compliance, and contractile performance can be observed, and seem to be compensated by enhanced atrial contribution of ventricular filling and prolongation of systole. However, little is known about the genetic regulatory mechanism underlying these changes.

Age-related changes throughout the cardiovascular system together with the high prevalence of cardiovascular diseases at older age predispose older adults to the development of chronic heart failure (CHF). In fact, CHF affects approximately 5 Million Americans, and over 500,000 new cases are reported each year.

We hope that the analysis of expression profiles at different ages together with the physiological and histological analysis, and subsequent comparison to expression profiles derived from heart failure models gives us new insight into the mechanisms of aging and its imlication in CHF.

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Experimental Design

To create a benchmark data set of expression profiles for normal FVB wildtype mice, we have collected the ventricular portion of the heart at the following stages:

• Embryonic day 12.5
• Neonatal day 1
• 1 week of age
• 4 weeks of age
• 3-5 months of age
• 1 year of age

For the embryonic stage, three hearts were pooled for each experiment. Two hearts were pooled at the neonatal stage. Adult hearts were analyzed individually. For adult mice at 3-5 months and one year of age, we have collected hearts separately for female and male mice. We did not discriminate between sex prepuberty. Phenotypic data include heart, lung, liver, and body weight at the time of sacrifice.

All FVB mice were obtained from Charles River laboratories.

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Page last modified: 07-Jun-2002