Myh6 promoter-driven Cre recombinase excises floxed DNA fragments in a subset of male germline cells.

Myh6-Cre transgenic mouse line was known to express Cre recombinase only in the heart. Nevertheless, during breeding Myh6-Cre to Rosa26fstdTom reporter (tdTom) mouse line, we observed that a significant part of their F2 tdTom/+ offspring had tdTom reporter gene universally activated. Our results show that Myh6-Cre transgenic mice have Cre recombinase activity in a subpopulation of the male germline cells, and that Myh6 gene transcripts are enriched in the interstitial Leydig cells and the undifferentiated spermatogonia stem cells. In summary, the current study confirms that the previously known "heart-specific" Myh6 promoter drives Cre expression in the testis.

Depletion of VGLL4 Causes Perinatal Lethality without Affecting Myocardial Development.

Congenital heart disease is one of the leading causes of pediatric morbidity and mortality, thus highlighting the importance of deciphering the molecular mechanisms that control heart development. As the terminal transcriptional effectors of the Hippo-YAP pathway, YAP and TEAD1 form a transcriptional complex that regulates the target gene expression and depletes either of these two genes in cardiomyocytes, thus resulting in cardiac hypoplasia. Vestigial-like 4 (VGLL4) is a transcriptional co-factor that interacts with TEAD and suppresses the YAP/TEAD complex by competing against YAP for TEAD binding. To understand the VGLL4 function in the heart, we generated two VGLL4 loss-of-function mouse lines: a germline Vgll4 depletion allele and a cardiomyocyte-specific Vgll4 depletion allele. The whole-body deletion of Vgll4 caused defective embryo development and perinatal lethality. The analysis of the embryos at day 16.5 revealed that Vgll4 knockout embryos had reduced body size, malformed tricuspid valves, and normal myocardium. Few whole-body Vgll4 knockout pups could survive up to 10 days, and none of them showed body weight gain. In contrast to the whole-body Vgll4 knockout mutants, cardiomyocyte-specific Vgll4 knockout mice had no noticeable heart growth defects and had normal heart function. In summary, our data suggest that VGLL4 is required for embryo development but dispensable for myocardial growth.