PMID- 18250097
OWN - NLM
STAT- MEDLINE
DCOM- 20080522
LR  - 20131121
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 17
IP  - 9
DP  - 2008 May 1
TI  - R-spondin1 plays an essential role in ovarian development through positively 
      regulating Wnt-4 signaling.
PG  - 1278-91
LID - 10.1093/hmg/ddn036 [doi]
AB  - In mammals, female development has traditionally been considered a default 
      process in the absence of the testis-determining gene, Sry. Recently, it has been 
      documented that the gene for R-spondin1 (RSPO1), a novel class of soluble 
      activator for Wnt/beta-catenin signaling, is mutated in two Italian families with 
      female-to-male (XX) sex reversal. To elucidate the role of Rspo1 as a candidate 
      female-determining gene in a mouse model, we generated Rspo1-null (Rspo1(-/-)) 
      mice and found that Rspo1(-/-) XX mice displayed masculinized features including 
      pseudohermaphroditism in genital ducts, depletion of fetal oocytes, male-specific 
      coelomic vessel formation and ectopic testosterone production in the ovaries. 
      Thus, although Rspo1 is required to fully suppress the male differentiation 
      program and to maintain germ cell survival during the development of XX gonads, 
      the loss of its activity has proved to be insufficient to cause complete XX sex 
      reversal in mice. Interestingly, these partial sex-reversed phenotypes of 
      Rspo1(-/-) XX mice recapitulated those of previously described Wnt-4(-/-) XX 
      mice. In accordance with this finding, the expression of Wnt-4 and its downstream 
      genes was deregulated in early Rspo1(-/-) XX gonads, suggesting that Rspo1 may 
      participate in suppressing the male pathway in the absence of Sry and maintaining 
      oocyte survival through positively regulating Wnt-4 signaling.
FAU - Tomizuka, Kazuma
AU  - Tomizuka K
AD  - Discovery Research Laboratories, Research Division, Kirin Pharma Co., Ltd., 
      Takasaki-shi, Gunma, 370-1295, Japan. ktomizuka@kirin.co.jp
FAU - Horikoshi, Kaori
AU  - Horikoshi K
FAU - Kitada, Rina
AU  - Kitada R
FAU - Sugawara, Yuriko
AU  - Sugawara Y
FAU - Iba, Yumi
AU  - Iba Y
FAU - Kojima, Ayako
AU  - Kojima A
FAU - Yoshitome, Akiko
AU  - Yoshitome A
FAU - Yamawaki, Kengo
AU  - Yamawaki K
FAU - Amagai, Mikiko
AU  - Amagai M
FAU - Inoue, Ayano
AU  - Inoue A
FAU - Oshima, Takeshi
AU  - Oshima T
FAU - Kakitani, Makoto
AU  - Kakitani M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080204
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Hormones, Ectopic)
RN  - 0 (RSPO1 protein, mouse)
RN  - 0 (Thrombospondins)
RN  - 0 (WNT4 protein, human)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt4 Protein)
RN  - 0 (Wnt4 protein, mouse)
RN  - 3XMK78S47O (Testosterone)
SB  - IM
MH  - Animals
MH  - Disorders of Sex Development/pathology/*physiopathology
MH  - Female
MH  - Fertility
MH  - Gene Expression Regulation, Developmental
MH  - Hormones, Ectopic/metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Models, Animal
MH  - Oocytes/cytology
MH  - Ovary/*growth & development/pathology/physiopathology
MH  - *Sex Differentiation
MH  - *Signal Transduction
MH  - Species Specificity
MH  - Testosterone/metabolism
MH  - Thrombospondins/*genetics/*metabolism
MH  - Wnt Proteins/genetics/*metabolism
MH  - Wnt4 Protein
EDAT- 2008/02/06 09:00
MHDA- 2008/05/23 09:00
CRDT- 2008/02/06 09:00
PHST- 2008/02/06 09:00 [pubmed]
PHST- 2008/05/23 09:00 [medline]
PHST- 2008/02/06 09:00 [entrez]
AID - ddn036 [pii]
AID - 10.1093/hmg/ddn036 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2008 May 1;17(9):1278-91. doi: 10.1093/hmg/ddn036. Epub 2008 Feb 
      4.