Highlights d Multiple nuclear factors affect selective transmission of mitochondrial genomes d Reducing mtDNA polymerase restricts the transmission of detrimental mtDNA mutants

Circadian rhythms are endogenously generated physiological and molecular rhythms with a cycle length of about 24 h. Bioluminescent reporters have been exceptionally useful for studying circadian rhythms in numerous species. Here, we report development of a reporter mouse generated by modification of a widely expressed and highly rhythmic gene encoding D-site albumin promoter binding protein ( Dbp). In this line of mice, firefly luciferase is expressed from the Dbp locus in a Cre recombinase-dependent manner, allowing assessment of bioluminescence rhythms in specific cellular populations. A mouse line in which luciferase expression was Cre-independent was also generated. The Dbp reporter alleles do not alter Dbp gene expression rhythms in liver or circadian locomotor activity rhythms. In vivo and ex vivo studies show the utility of the reporter alleles for monitoring rhythmicity. Our studies reveal cell-type-specific characteristics of rhythms among neuronal populations within the suprachiasmatic nuclei ex vivo. In vivo studies show Dbp-driven bioluminescence rhythms in the liver of Albumin-Cre;Dbp KI/+ “liver reporter” mice. After a shift of the lighting schedule, locomotor activity achieved the proper phase relationship with the new lighting cycle more rapidly than hepatic bioluminescence did. As previously shown, restricting food access to the daytime altered the phase of hepatic rhythmicity. Our model allowed assessment of the rate of recovery from misalignment once animals were provided with food ad libitum. These studies confirm the previously demonstrated circadian misalignment following environmental perturbations and reveal the utility of this model for minimally invasive, longitudinal monitoring of rhythmicity from specific mouse tissues.

Circadian rhythms are daily oscillations in physiology and behavior that can be assessed by recording body temperature, locomotor activity, or bioluminescent reporters, among other measures. These different types of data can vary greatly in waveform, noise characteristics, typical sampling rate, and length of recording. We developed 2 Shiny apps for exploration of these data, enabling visualization and analysis of circadian parameters such as period and phase. Methods include the discrete wavelet transform, sine fitting, the Lomb-Scargle periodogram, autocorrelation, and maximum entropy spectral analysis, giving a sense of how well each method works on each type of data. The apps also provide educational overviews and guidance for these methods, supporting the training of those new to this type of analysis. CIRCADA-E (Circadian App for Data Analysis–Experimental Time Series) allows users to explore a large curated experimental data set with mouse body temperature, locomotor activity, and PER2::LUC rhythms recorded from multiple tissues. CIRCADA-S (Circadian App for Data Analysis–Synthetic Time Series) generates and analyzes time series with user-specified parameters, thereby demonstrating how the accuracy of period and phase estimation depends on the type and level of noise, sampling rate, length of recording, and method. We demonstrate the potential uses of the apps through 2 in silico case studies.