title: New evidence confirms that the mitochondrial bottleneck is generated without reduction of mitochondrial DNA content in early primordial germ cells of mice.
abstract: In mammals, observations of rapid shifts in mitochondrial DNA (mtDNA) variants between generations have led to the creation of the bottleneck theory for the transmission of mtDNA. The bottleneck could be attributed to a marked decline of mtDNA content in germ cells giving rise to the next generation, to a small effective number of mtDNA segregation units resulting from homoplasmic nucleoids rather than the single mtDNA molecule serving as the units of segregation, or to the selective transmission of a subgroup of the mtDNA population to the progeny. We have previously determined mtDNA copy number in single germ cells and shown that the bottleneck occurs without the reduction in germline mtDNA content. Recently one study suggested that the bottleneck is driven by a remarkable decline of mtDNA copies in early primordial germ cells (PGCs), while another study reported that the mtDNA genetic bottleneck results from replication of a subpopulation of the mtDNA genome during postnatal oocyte maturation and not during embryonic oogenesis, despite a detected a reduction in mtDNA content in early PGCs. To clarify these contradictory results, we examined the mtDNA copy number in PGCs isolated from transgenic mice expressing fluorescent proteins specifically in PGCs as in the aforementioned two other studies. We provide clear evidence to confirm that no remarkable reduction in mtDNA content occurs in PGCs and reinforce that the bottleneck is generated without reduction of mtDNA content in germ cells.
authors.affiliation: Laboratory of Mouse Models for Human Heritable Diseases, The Tokyo Metropolitan Institute of Medical Science (Rinshoken), Tokyo, Japan.
authors.forename: Liqin
authors.initials: L
authors.lastname: Cao
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shitara
authors.forename: Michihiko
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Hayashi
authors.forename: Kuniya
authors.initials: K
authors.lastname: Abe
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yonekawa
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002469:Cell Separation; D002868:Chromosomal Proteins, Non-Histone; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000235:genetics*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D013194:Staining and Labeling; D014157:Transcription Factors / Q000378:metabolism; D000097573:Red Fluorescent Protein
chemical_list: D000469:Alkaline Phosphatase; D015415:Biomarkers; D002868:Chromosomal Proteins, Non-Histone; D004272:DNA, Mitochondrial; D008164:Luminescent Proteins; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins; D014157:Transcription Factors; D000097573:Red Fluorescent Protein; C462180:Dppa3 protein, mouse; C513258:Prdm1 protein, mouse