Decreased physical performance of congenic mice with mismatch between the nuclear and the mitochondrial genome.

Nagao, Yoshimi; Totsuka, Yoshikazu; Atomi, Yoriko; Kaneda, Hideki; Lindahl, Kirsten Fischer; Imai, Hiroshi; Yonekawa, Hiromichi

doi:10.1266/ggs.73.21

Cited by 95 publications

(65 citation statements)

References 29 publications

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“…Recent studies have shown that polymorphisms in the mitochondrial DNA (mtDNA) may influence the phenotype of inbred animals with identical nuclear genetic background (Johnson et al, 2001;Nagao et al, 1998;Roubertoux et al, 2003 has been shown that neurofibromin, the protein affected by mutations in the NF1-gene, partially colocalizes with mitochondria thus suggesting a functional link (Roudebush et al, 1997). The mtDNA is therefore an obvious candidate for an extrachromosomal phenotype modifier.…”

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confidence: 99%

Analysis of Mitochondrial DNA in Discordant Monozygotic Twins With Neurofibromatosis Type 1

et al. 2007

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Neurofibromatosis type 1 (NF1) is the most frequent neurocutaneous disorder with autosomal dominant inheritance. Phenotype variability is high ranging from merely several café-au-lait spots to malignant peripheral nerve sheath tumors or severe disfigurement through plexiform neurofibromas. Identification of genetic factors that modify the NF1 phenotype would contribute to the understanding of NF1 pathophysiology and improve patient counselling. As even monozygotic (MZ) twins with NF1 may differ phenotypically, we wondered whether these variations might be inherited in a non-Mendelian fashion. Mitochondrial DNA (mtDNA) is inherited extrachromosomally through the cytoplasm of the oocyte and often harbours heteroplasmic sequence variations. At the time of blastomere separation, these variants may be skewedly distributed and effect phenotypic differences. Because of their co-localization with the tumor suppressor protein neurofibromin, which is mutated in NF1, mitochondria were particular attractive candidates for investigation. MtDNA was extracted from nucleated blood cells of four pairs of discordant MZ twins with NF1 and from cutaneous neurofibromas of one twin pair. We sequenced the entire mitochondrial genome and determined the state of heteroplasmy by investigating a microsatellite region of the mitochondrial D-loop (D310-tract). The clinical diagnosis was confirmed in all patients by detection of pathogenic mutations in the NF1 gene. Monozygosity was verified by genotyping. However, we did not detect evidence for mtDNA sequence differences or for different degrees of heteroplasmy between individuals of the same twin pair. The phenotypic discordance of MZ twins with NF1 cannot be explained by skewed distribution of mtDNA mutations or polymorphisms.

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confidence: 99%

Analysis of Mitochondrial DNA in Discordant Monozygotic Twins With Neurofibromatosis Type 1

et al. 2007

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“…Congenic cloned mice derived from these interspecific NT embryos with mismatch (functional asynchrony) between the nuclear and mitochondrial genome had decreased physical performances. Results of the studies by Nagao et al (1998) also confirmed that the cytoplast-inherited mtDNA component can be responsible, to a high degree, for non-coordinated nuclear-ooplasmic interactions between maternal transcripts and/or proteins and donor nuclear factors. Together these are defined as genomic discordance between nuclear (donor cell-or karyoplast-mediated) and extranuclear (recipient cell-or ooplast-mediated) inheritance in clonal cytoplasmic hybrids.…”

Section: Cytoplasmic (Extranuclear) Inheritance and Different Patternmentioning

confidence: 69%

“…No pregnancies occurred following transfer into foster mothers (Dominko et al, 1999), indicating that the incompatibility of nuclear DNA-and mitochondrial DNA-encoded components (both transcripts such as mRNA, tRNA, rRNA molecules and protein products) from different species is likely to inhibit normal embryogenesis and foetogenesis. Moreover, Nagao et al (1997Nagao et al ( , 1998 have demonstrated the deleterious effect of heterogeneous mtDNA copies on in vitro developmental potential of mouse embryos produced by xenonuclear transfer of Mus spretus donor cell nuclei into Mus musculus oocyte cytoplasm. Congenic cloned mice derived from these interspecific NT embryos with mismatch (functional asynchrony) between the nuclear and mitochondrial genome had decreased physical performances.…”

Section: Cytoplasmic (Extranuclear) Inheritance and Different Patternmentioning

confidence: 99%

The effect of mitochondrial genome on architectural remodeling and epigenetic reprogramming of donor cell nuclei in mammalian nuclear transfer-derived embryos

Samiec¹

2005

J. Anim. Feed Sci.

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There are some species-specific epigenetic factors present in the oocyte cytoplasm that may contribute to nucleo-cytoplasmic incompatibilities either immediately after nuclear transfer (NT) or at later stages of development. These potential incompatibilities will affect, to some degree, the ultimate utility of NT technology. It has been demonstrated that maternally inherited mitochondrial DNA molecules (mtDNAs) accumulated in the mitochondrial reservoirs of recipient-oocyte cytosol play an important role in nuclear-ooplasmic asynchrony. This asynchrony involves the incompatibility in epigenetic modifications of somatic genome supporting the developmental program of reconstituted cybrids. It also involves incompatibility in molecular mechanisms controlling the karyokinesis and cytokinesis restriction points responsible for coordinated pseudomeiotic to mitotic cycle transition following activation of the reconstituted oocyte. Moreover, the presence of oocyte-derived mitochondrial genetic apparatus influences clonal embryo implantation. For that reason, the deleterious effect on preimplantation development of NT embryos of heterogeneous mtDNA sources arising from possible mitochondrial heteroplasmy in the reconstructed nuclear-cytoplasmic hybrids, should not be discounted. That is why, the production of nuclear transfer embryos, foetuses and offspring with precisely defined constellations of nuclear and/or mitochondrial genome can be valuable for experimentally dissecting the effects of nuclear and cytoplasmic genetic/epigenetic components as well as the intrauterine environment on embryonic, foetal, and postnatal development of cloned individuals.

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“…Body mass, whole-organism and mass-specific basal metabolic rate (BMR), and mass-specific cold-induced metabolic rate (MR c ) for 3 species and 2 hybrid crosses of Onychomys would uncover respiratory defects in F 1 hybrids. For example, while gross metabolic function is normal in Mus musculus domesticusderived lab mice with mitochondria from a closely related congener, Mus spretus (McKenzie et al, 2004), these mitochondrial hybrids (cybrids) tire faster than controls in a running to exhaustion test (Nagao et al, 1998). A 2-fold excess in lactate production indicative of inefficient cellular metabolism may explain cybrid physical performance deficits (McKenzie et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Asymmetric energetic costs in reciprocal-cross hybrids between carnivorous mice (Onychomys)

Shipley

Campbell

Searle

et al. 2016

Journal of Experimental Biology

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Aerobic respiration is a fundamental physiological trait dependent on coordinated interactions between gene products of the mitochondrial and nuclear genomes. Mitonuclear mismatch in interspecific hybrids may contribute to reproductive isolation by inducing reduced viability (or even complete inviability) due to increased metabolic costs.However, few studies have tested for effects of mitonuclear mismatch on respiration at the whole-organism level. We explored how hybridization affects metabolic rate in closely related species of grasshopper mice (genus Onychomys) to better understand the role of metabolic costs in reproductive isolation. We measured metabolic rate across a range of temperatures to calculate basal metabolic rate (BMR) and cold-induced metabolic rate (MR c ) in O. leucogaster, O. torridus and O. arenicola, and in reciprocal F 1 hybrids between the latter two species. Within the genus, we found a negative correlation between mass-specific BMR and body mass. Although O. arenicola was smaller than O. torridus, hybrids from both directions of the cross resembled O. arenicola in body mass. In contrast, hybrid BMR was strongly influenced by the direction of the cross: reciprocal F 1 hybrids were different from each other but indistinguishable from the maternal species. In addition, MR c was not significantly different between hybrids and either parental species. These patterns indicate that metabolic costs are not increased in Onychomys F 1 hybrids and, while exposure of incompatibilities in F 2 hybrids cannot be ruled out, suggest that mitonuclear mismatch does not act as a primary barrier to gene flow. Maternal matching of BMR is suggestive of a strong effect of mitochondrial genotype on metabolism in hybrids. Together, our findings provide insight into the metabolic consequences of hybridization, a topic that is understudied in mammals.

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Decreased physical performance of congenic mice with mismatch between the nuclear and the mitochondrial genome.

Cited by 95 publications

References 29 publications

Analysis of Mitochondrial DNA in Discordant Monozygotic Twins With Neurofibromatosis Type 1

Analysis of Mitochondrial DNA in Discordant Monozygotic Twins With Neurofibromatosis Type 1

The effect of mitochondrial genome on architectural remodeling and epigenetic reprogramming of donor cell nuclei in mammalian nuclear transfer-derived embryos

Asymmetric energetic costs in reciprocal-cross hybrids between carnivorous mice (Onychomys)

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