Sox3 is required for gonadal function, but not sex determination, in males and females.
Sox3 is expressed in developing gonads and in the brain. Evolutionary evidence suggests that the X-chromosomal Sox3 gene may be the ancestral precursor of Sry, a sex-determining gene, and Sox3 has been proposed to play a role in sex determination. However, patients with mutations in SOX3 exhibit normal gonadal determination but are mentally retarded and have short stature secondary to growth hormone (GH) deficiency. We used Cre-LoxP targeted mutagenesis to delete Sox3 from mice. Null mice of both sexes had no overt behavioral deficits and exhibited normal GH gene expression. Low body weight was observed for some mice; overgrowth and misalignment of the front teeth was observed consistently. Female Sox3 null mice (-/-) developed ovaries but had excess follicular atresia, ovulation of defective oocytes, and severely reduced fertility. Pituitary (luteinizing hormone and follicle-stimulating hormone) and uterine functions were normal in females. Hemizygous male null mice (-/Y) developed testes but were hypogonadal. Testis weight was reduced by 42%, and there was extensive Sertoli cell vacuolization, loss of germ cells, reduced sperm counts, and disruption of the seminiferous tubules. We conclude that Sox3 is not required for gonadal determination but is important for normal oocyte development and male testis differentiation and gametogenesis.
Department of Medicine, Feinberg School of Medicine, Northwestern University, 251 East Huron Street, Chicago, IL 60611, USA.
Jeffrey
J
Weiss
Joshua J
JJ
Meeks
Lisa
L
Hurley
Gerald
G
Raverot
Andrea
A
Frassetto
J Larry
JL
Jameson
D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005260:Female; D018390:Gene Targeting; D006130:Growth Disorders / Q000235:genetics; D013006:Growth Hormone / Q000235:genetics; D006609:High Mobility Group Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D007247:Infertility, Female / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009866:Oogenesis / Q000235:genetics; D010053:Ovary / Q000002:abnormalities / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors; D019849:Sex Determination Processes; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis / Q000002:abnormalities / Q000502:physiology*; D014071:Tooth Abnormalities / Q000235:genetics; D014157:Transcription Factors; D014960:X Chromosome / Q000235:genetics
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D012333:RNA, Messenger; D055748:SOXB1 Transcription Factors; C527786:Sox3 protein, mouse; D014157:Transcription Factors; D013006:Growth Hormone