Novel Jbts17 mutant mouse model of Joubert syndrome with cilia transition zone defects and cerebellar and other ciliopathy related anomalies.

Recent studies identified a previously uncharacterized gene C5ORF42 (JBTS17) as a major cause of Joubert syndrome (JBTS), a ciliopathy associated with cerebellar abnormalities and other birth defects. Here we report the first Jbts17 mutant mouse model, Heart Under Glass (Hug), recovered from a forward genetic screen. Exome sequencing identified Hug as a S235P missense mutation in the mouse homolog of JBTS17 (2410089e03rik).

Interrogating congenital heart defects with noninvasive fetal echocardiography in a mouse forward genetic screen.

Background: Congenital heart disease (CHD) has a multifactorial pathogenesis, but a genetic contribution is indicated by heritability studies. To investigate the spectrum of CHD with a genetic pathogenesis, we conducted a forward genetic screen in inbred mice using fetal echocardiography to recover mutants with CHD. Mice are ideally suited for these studies given that they have the same four-chamber cardiac anatomy that is the substrate for CHD.

IFT25 links the signal-dependent movement of Hedgehog components to intraflagellar transport.

The intraflagellar transport (IFT) system is required for building primary cilia, sensory organelles that cells use to respond to their environment. IFT particles are composed of about 20 proteins, and these proteins are highly conserved across ciliated species. IFT25, however, is absent from some ciliated organisms, suggesting that it may have a unique role distinct from ciliogenesis.

Mitochondrial nucleoids undergo remodeling in response to metabolic cues.

Mitochondrial DNA is organized as a nucleoprotein complex called the nucleoid. Its major protein components have been identified in different organisms, but it is yet unknown whether nucleoids undergo any form of remodeling. Using an in organello ChIP-on-chip assay, we demonstrate that the DNA-bending protein Abf2 binds to most of the mitochondrial genome with a preference for GC-rich gene sequences.