title: The hotei mutation of medaka in the anti-Mullerian hormone receptor causes the dysregulation of germ cell and sexual development.
abstract: We previously performed mutant screens in the medaka for defects in gonadal development and identified a mutant of interest in this regard, which was designated as hotei (hot). This mutant manifests a number of remarkable phenotypic abnormalities including: (i) excessive proliferation of germ cells that initiates at around the hatching stage regardless of the genetic sex of the fish; (ii) initiation of premature meiosis in phenotypically male hot homozygotes; (iii) one-half of the hot-homozygous XY fish undergo sex reversal, which accompanies the expression of the female-characteristic aromatase gene in the somatic cells of the gonad; and (iv) in phenotypically female homozygotes, follicular development is arrested at an early stage. We have also performed genetic mapping, chromosome walking, and candidate gene sequencing analysis of hot and demonstrate that the underlying mutation occurs in the recently identified medaka anti-Müllerian hormone (Amh) receptor type II (amhrII) gene. Moreover, this gene was found to be responsible for each of the hot phenotypes, as an amhrII transgene rescues these abnormalities. In addition, the amhrII gene is expressed in the somatic cells of the gonads of both sexes. The phenotypes of the hot homozygotes indicate that there are multiple regulatory functions of the AMH/AMHRII signaling system in the development of the gonad, including the sex-dependent regulation of germ cell proliferation and follicular development. These presumably represent the basic roles of Amh, which precede Müllerian duct evolution during phylogeny.
authors.affiliation: Japan Science and Technology Agency, Solution Oriented Research for Science and Technology Kondoh Research Team, Kyoto 606-8305, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Morinaga
authors.forename: Daisuke
authors.initials: D
authors.lastname: Saito
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nakamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Shuichi
authors.initials: S
authors.lastname: Asakawa
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitani
authors.forename: Makoto
authors.initials: M
authors.lastname: Furutani-Seiki
authors.forename: Minoru
authors.initials: M
authors.lastname: Tanaka
authors.forename: Hisato
authors.initials: H
authors.lastname: Kondoh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D001483:Base Sequence; D016386:Chromosome Walking; D017931:DNA Primers; D005260:Female; D005854:Germ Cells / Q000254:growth & development*; D006066:Gonads / Q000378:metabolism; D057850:Hermaphroditic Organisms; D017403:In Situ Hybridization; D008297:Male; D008540:Meiosis / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009990:Oryzias / Q000235:genetics*; D006080:Ovarian Follicle / Q000254:growth & development; D010641:Phenotype; D018000:Receptors, Peptide / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D019849:Sex Determination Processes; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D017931:DNA Primers; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; C084621:anti-Mullerian hormone receptor; D001141:Aromatase