Mitochondrial DNA and Functional Investigations into the Radiosensitivity of Four Mouse Strains

Abstract

We investigated whether genetic radiosensitivity-related changes in mtDNA/nDNA ratios are significant to mitochondrial function and if a material effect on mtDNA content and function exists. BALB/c (radiosensitive), C57BL/6 (radioresistant), and F1 hybrid mouse strains were exposed to total body irradiation. Hepatic genomic DNA was extracted, and mitochondria were isolated. Mitochondrial oxygen consumption, ROS, and calcium-induced mitochondrial swelling were measured. Radiation influenced strain-specific survival in vivo. F1 hybrid survival was influenced by maternal input. Changes in mitochondrial content corresponded to survival in vivo among the 4 strains. Calcium-induced mitochondrial swelling was strain dependent. Isolated mitochondria from BALB/c mice were significantly more sensitive to calcium overload than mitochondria from C57BL/6 mice. Maternal input partially influenced the recovery effect of radiation on calcium-induced mitochondrial swelling in F1 hybrids; the hybrid with a radiosensitive maternal lineage exhibited a lower rate of recovery. Hybrids had a survival rate that was biased toward maternal input. mtDNA content and mitochondrial permeability transition pores (MPTP) measured in these strains before irradiation reflected a dominant input from the parent. After irradiation, the MPTP opened sooner in radiosensitive and hybrid strains, likely triggering intrinsic apoptotic pathways. These findings have important implications for translation into predictors of radiation sensitivity/resistance.

Mitochondrial Respiration in Outer Retina Contributes to Light-Evoked Increase in Hydration In Vivo

“…19,33–35 The energy bionetwork is important in this regard because it regulates large light-driven swings in photoreceptor ATP production, which is required to support phototransduction and modify ion channel function and outer retina ion content. 19,36–44 In support of this view, mice genetically modified to prevent phototransduction exhibit no OCT and diffusion MRI responses. 4,7 The results presented here support this energy ecosystem concept, but additional work is needed to determine, for example, the differences in mitochondria morphology, density, or function between C57BL/6 and 129S6/SvEvTac mice.…”

Innate Mucosal Immune System Response of BALB/c vs C57BL/6 Mice to Injury in the Setting of Enteral and Parenteral Feeding

“…However, different inbred mouse strains may demonstrate different phenotypic responses to the same independent variables 18 . ‐ 21 , 34 ‐ 40 This work shows that 2 commonly used strains of inbred mice, BALB/c and C57BL/6, display dramatically different mucosal immunologic stress responses to injury, highlighting the importance of choosing an appropriate background strain of mice for relevant study. In this work, we examined whether BALB/c or C57BL/6 mice immunologically resemble the respiratory and intestinal mucosal immune responses to injury noted to occur in humans and outbred ICR mice 1 .…”

“…Other works link differences in cytokine and chemokine expression to phenotypic variations in inflammatory and cancer responses of these 2 mouse strains 34 , 36 , 56 . ‐ 61 For instance, BALB/c mice prove more fibrosis resistant, radiosensitive, and cancer susceptible than their C57BL/6 counterparts, again highlighting the power of the dampened cytolytic potential seen in Th2‐predominant mice, providing an attractive explanation for divergent phenotypes 38 , 56 , 62 . Recent speculation also suggests that differences in gut microbial composition between inbred mouse strains contribute to differences in metabolic, inflammatory, and immune states independent of experimental variables 63 .…”

The Lowest Radiation Dose Having Molecular Changes in the Living Body

“… 63 Another study examined the effects of 7 Gy of total-body γ-irradiation from a 137 Cs source on mitochondrial DNA. 64 The findings obtained from the 4 strains investigated BALB/c, C57BL/6, and F1 hybrid (BALB/c female × C57BL/6 male and BALB/c male × C57BL/6 female), indicating that calcium-induced mitochondrial swelling was strain dependent and mitochondrial permeability transition pores opened sooner in radiosensitive strains ( Table 2 ).…”