Loss of the protein NUPR1 (p8) leads to delayed LHB expression, delayed ovarian maturation, and testicular development of a sertoli-cell-only syndrome-like phenotype in mice.
The high mobility group factor NUPR1, also known as p8 and com1, plays a role in temporal expression of the beta subunit of luteinizing hormone, LHB, during gonadotroph development. At Embryonic Day (e) 16.5, LHB is detectable in wild-type (Nupr1(+/+)) but not Nupr1 knockout (Nupr1(-/-)) mice. LHB is initiated by e17.5 in Nupr1(-/-) mice, and expression is fully recovered by Postnatal Day (p) 2. Factors indicative of pituitary maturation, GATA2, CGA, and TSH, are not differentially expressed in Nupr1(-/-) and Nupr1(+/+) embryos at e17.5. Therefore, the delay in LHB expression does not appear to result from delayed pituitary development. In addition, the role of NUPR1 in gonadotropin expression appears specific for LHB, as no difference in FSHB is observed in Nupr1(-/-) and Nupr1(+/+) embryos. The gonads are also impacted by the absence of NUPR1. Ovaries of female Nupr1(-/-) mice lack corpora lutea (CL) at 8 wk, an age at which CL are present in all Nupr1(+/+) littermates. Sexual maturity is recovered by 11 wk in Nupr1(-/-) mice. Conversely, the testes of Nupr1(-/-) males appear normal through 8 mo of age. By 10 mo, however, these mice develop a condition in which a significant number of seminiferous tubules lack germ cells, an abnormality reminiscent of human Sertoli-cell-only syndrome. NUPR1 is undetectable in Nupr1(+/+) gonadotrophs by p2 and remains absent in adulthood, but quantitative PCR analysis indicates Nupr1(+/+) adult ovaries and testes express Nupr1 mRNA. Therefore, the ovarian and testicular phenotypes may be due to the loss of NUPR1 directly at the gonads.
Million Passe
Christina M
CM
Medical Sciences Program, Indiana University School of Medicine, Bloomington, Indiana 47405, USA.
White
Crystal R
CR
King
Michael W
MW
Quirk
Phillip L
PL
Iovanna
Juan L
JL
Quirk
Christine C
CC
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D004622:Embryo, Mammalian; D005260:Female; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D052681:Gonadotrophs / Q000378:metabolism / Q000502:physiology; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D010053:Ovary / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D010902:Pituitary Gland / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D054331:Sertoli Cell-Only Syndrome / Q000235:genetics* / Q000473:pathology; D012741:Sexual Maturation / Q000235:genetics / Q000502:physiology; D013737:Testis / Q000196:embryology / Q000254:growth & development / Q000473:pathology*; D014018:Tissue Distribution
D004268:DNA-Binding Proteins; D037201:Follicle Stimulating Hormone, beta Subunit; D037101:Luteinizing Hormone, beta Subunit; D009363:Neoplasm Proteins; C491644:Nupr1 protein, mouse