Species: mouse
Mutation name:
type: null mutation
fertility: subfertile
Comment: Mitoguardin-1 and -2 promote maturation and the developmental potential of mouse oocytes by maintaining mitochondrial dynamics and functions. Liu XM et al. (2016) Mitochondrial dynamics change mitochondrial morphological features and numbers as a part of adaptive cellular metabolism, which is vital for most eukaryotic cells and organisms. A disease or even death of an animal can occur if these dynamics are disrupted. Using large-scale genetic screening in fruit flies, we previously found the gene mitoguardin (Miga), which encodes a mitochondrial outer-membrane protein and promotes mitochondrial fusion. Knockout mouse strains were generated for the mammalian Miga homologs Miga1 and Miga2. Miga1/2-/- females show greatly reduced quality of oocytes and early embryos and are subfertile. Mitochondria became clustered in the cytoplasm of oocytes from the germinal-vesicle stage to meiosis II; production of reactive oxygen species increased in mitochondria and caused damage to mitochondrial ultrastructures. Additionally, reduced ATP production, a decreased mitochondrial-DNA copy number, and lower mitochondrial membrane potential were detected in Miga1/2-/- oocytes during meiotic maturation. These changes resulted in low rates of polar-body extrusion during oocyte maturation, reduced developmental potential of the resulting early embryos, and consequently female subfertility. We provide direct evidence that MIGA1/2-regulated mitochondrial dynamics is crucial for mitochondrial functions, ensure oocyte maturation, and maintain the developmental potential.//////////////////

Species: mouse
Mutation name:
type: null mutation
fertility: subfertile
Comment: Mitochondrial Function Regulated by Mitoguardin-1/2 is Crucial for Ovarian Endocrine Functions and Ovulation. Liu XM et al. (2017) The balances of mitochondrial dynamic changes, mitochondrial morphology, and mitochondrial number are critical in cell metabolism. Once disturbed, disorders in these processes generally cause diseases or even death in animals. We performed large-scale genetic screenings in fruit flies and discovered the new gene mitoguardin (miga) that encodes for a mitochondrial outer membrane protein. In order to examine the physiological functions of its mammalian homologs Miga1 and 2, we generated Miga1 and Miga2 single- and double-knockout mouse strains and found that the knockout mice were viable, but the females were subfertile. The ovarian phenotypes of these mice suggested that the MIGA1/2 proteins play an important role in ovulation and ovarian steroidogenesis. In vivo and in vitro analyses of Miga1/2-knockout granulosa cells showed severe defects in luteinization and steroidogenesis and disordered mitochondrial morphology and function in response to gonadotropins. This is the first report of genes involved in mitochondrial fusion and morphology regulating mitochondrial functions during ovulation and luteinization. These results suggest a new mechanism of gonadotropin-regulated ovarian endocrine functions and provide clues for therapeutic treatments of infertile females.//////////////////