Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development.
FOXL2 mutations cause gonadal dysgenesis or premature ovarian failure (POF) in women, as well as eyelid/forehead dysmorphology in both sexes (the 'blepharophimosis-ptosis-epicanthus inversus syndrome', BPES). Here we report that mice lacking Foxl2 recapitulate relevant features of human BPES: males and females are small and show distinctive craniofacial morphology with upper eyelids absent. Furthermore, in mice as in humans, sterility is confined to females. Features of Foxl2 null animals point toward a new mechanism of POF, with all major somatic cell lineages failing to develop around growing oocytes from the time of primordial follicle formation. Foxl2 disruption thus provides a model for histogenesis and reproductive competence of the ovary.
Uda
Manuela
M
Laboratory of Genetics, National Institute on Aging, Baltimore, MD 21224, USA.
Ottolenghi
Chris
C
Crisponi
Laura
L
Garcia
Jose Elias
JE
Deiana
Manila
M
Kimber
Wendy
W
Forabosco
Antonino
A
Cao
Antonio
A
Schlessinger
David
D
Pilia
Giuseppe
G
D000818:Animals; D016569:Blepharophimosis / Q000209:etiology / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000473:pathology; D005143:Eyelids / Q000002:abnormalities; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D017353:Gene Deletion; D007120:Immunochemistry; D019394:Ki-67 Antigen / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010053:Ovary / Q000196:embryology / Q000254:growth & development / Q000473:pathology*; D016649:Primary Ovarian Insufficiency / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
D004268:DNA-Binding Proteins; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; C498893:Foxl2 protein, mouse; D019394:Ki-67 Antigen; D014157:Transcription Factors