The expression of NPPA splice variants during mouse cardiac development

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• Developmental Biology

Background:

• Natriuretic peptide precursor-A (NPPA) encodes atrial natriuretic peptide (ANP), a crucial marker for embryonic heart development.
• While human NPPA exhibits alternative splicing, no such variants were previously reported in mice.
• Investigating NPPA gene expression is vital for understanding cardiac differentiation and development.

Purpose of the Study:

• To explore the expression patterns of the NPPA gene during the cardiac differentiation of mouse adipose-tissue-derived stem cells (ADSCs) and embryonic stem (ES) cells.
• To identify and characterize alternatively spliced variants of NPPA in mouse models.
• To determine the role of NPPA isoforms in early cardiogenesis and adult cardiac tissue.

Main Methods:

• Reverse-transcription polymerase chain reaction (RT-PCR) was employed to analyze NPPA gene expression.
• Cardiac differentiation was induced in mouse ADSCs and ES cells.
• NPPA expression was examined in embryonic mouse hearts and mature cardiomyocytes.

Main Results:

• Cardiac-specific markers, including ANP, were detected in differentiated cells.
• Three novel intron-retained splice variants of NPPA were identified during ADSC and ES cell cardiac differentiation.
• These intron-retained NPPA variants were also found in early embryonic mouse hearts and freshly isolated stromal vascular fraction of adipose tissue.
• Only the canonical NPPA isoform was observed in mature cardiomyocytes of 1-week-old mice.

Conclusions:

• The study provides the first evidence of intron-retained NPPA mRNA splice variants during early mouse cardiogenesis.
• These variants are also expressed in mouse adipose tissue, suggesting a broader role for NPPA.
• Findings contribute to a deeper understanding of NPPA gene regulation and its significance in cardiac development and tissue biology.