Abstract

Cardiac repair following injury is restricted due to restrained ability of the cardiomyocyte to proliferate. Therefore, it is important to explore different approaches to facilitate de novo cardiomyocyte regeneration. CDKN1A interacting zinc finger protein 1 (Ciz1) is a recently identified gene that has been shown to play a critical role in mammalian DNA replication. The protein localises to dynamic sub-nuclear foci (replication factories). Ciz1 expression has been detected in all mammalian cell lines tested to date, including differentiated and embryonic stem cells, and roles for Ciz1 in cell differentiation and proliferation have been indicated. Furthermore Ciz1 and its splice variants have been linked to proliferative disorders, including cancer. However, Ciz1 is also expressed at low levels in terminally differentiated cells such as adult cardiomyocytes suggesting additional functions of the protein on top of its characterised role in DNA replication. This study aims to investigate the role of Ciz1 in cardiomyocytes through development of a conditional transgenic Ciz1 over-expression mouse model. Transgenic hearts from 3 to 10 week old mice are enlarged due to cardiomyocyte hyperplasia, associated with altered nuclear dynamics. The results suggest that Ciz1 may represent a suitable novel candidate for therapeutic application in cardiovascular disease.