A natural loss-of-function deletion of the cytohesin 1 (Cyth1) gene in BALB/cByJ mice does not impact cardiomyocyte polyploidy

TL;DR

A natural deletion in the Cyth1 gene in BALB/cByJ mice does not affect heart cell polyploidy, suggesting Cyth1 is not a key driver of this process.

Contribution

The study shows that a natural Cyth1 deletion in BALB/cByJ mice does not influence cardiomyocyte ploidy, challenging its role in this process.

Findings

A large deletion in the Cyth1 gene in BALB/cByJ mice creates a null allele.

Absence of Cyth1 does not impact cardiomyocyte polyploidy in mice.

Ectopic transcription of Dnah17 occurs but likely does not produce a functional protein.

Abstract

Mammalian cardiomyocytes (CMs) mostly become polyploid shortly after birth. Because this feature may relate to several aspects of heart biology, including regeneration after injury, the mechanisms that cause polyploidy are of interest. BALB/cJ and BALB/cByJ mice are highly related sister strains that diverge substantially in CM ploidy. We identified a large deletion in the Cyth1 gene that arose uniquely in BALB/cByJ mice that creates a null allele. The deletion also results in ectopic transcription of the downstream gene Dnah17, although this transcript is unlikely to encode a protein. By evaluating the natural null allele from BALB/cByJ and an engineered knockout allele in the C57BL/6J background, we determined that absence of Cyth1 does not by itself influence CM ploidy. The ready availability of BALB/cByJ mice may be helpful to other investigations of Cyth1 in other biological processes.

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