{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T17:24:59Z","timestamp":1789925099008,"version":"4.0.1"},"reference-count":38,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:p>\n                  <jats:bold>Background:<\/jats:bold> Delayed puberty is common among individuals with cystic fibrosis (CF) and is usually attributed to chronic disease and\/or poor nutrition. However, it has recently been recognised that pubertal delay can occur even in the setting of good nutritional and clinical status. This finding, along with evidence that <jats:italic>Cftr<\/jats:italic> is expressed in rat brain, human hypothalamus, and a gonadotropin releasing hormone secreting cell line, raises the possibility that some of the pubertal delay in CF could stem directly from alterations in <jats:italic>Cftr<\/jats:italic> function that affect the hypothalamic-pituitary-gonadal axis.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methods:<\/jats:bold> To examine this hypothesis, we investigated pubertal timing (as assessed by vaginal opening (VO)) in a mouse model of CF (<jats:italic>Cftr<jats:sup>tm1Unc<\/jats:sup>\n                  <\/jats:italic>) engineered to produce a truncated <jats:italic>Cftr<\/jats:italic> mRNA and referred to as S489X. Homozygous knockout, heterozygote, and wild type (WT) female mice were examined.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results:<\/jats:bold> As expected, the S489X<jats:sup>\u2212<\/jats:sup>\/S489X<jats:sup>\u2212<\/jats:sup> knockout mice, which have chronic inflammation and gastrointestinal disease, grew more slowly and had later onset of puberty than WT animals. We anticipated that the S489X<jats:sup>\u2212<\/jats:sup>\/S489X<jats:sup>+<\/jats:sup> heterozygotes, which have no clinical CF phenotype, might display an intermediate timing of puberty. Surprisingly, however, these mice had earlier VO than WT. These findings were confirmed in a second, independent model of CF engineered to generate the \u0394F508 mutation in mice. Again, the homozygotes displayed later pubertal timing, while the heterozygotes displayed earlier VO than the WT animals.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusions:<\/jats:bold> These data provide further evidence that <jats:italic>Cftr<\/jats:italic> can directly modulate the reproductive endocrine axis and raise the possibility that heterozygate mutation carriers may have a reproductive advantage.<\/jats:p>","DOI":"10.1136\/jmg.2005.032839","type":"journal-article","created":{"date-parts":[[2006,6,1]],"date-time":"2006-06-01T17:28:21Z","timestamp":1149182901000},"page":"e29-e29","source":"Crossref","is-referenced-by-count":26,"title":["The cystic fibrosis transmembrane conductance regulator (<i>Cftr<\/i>) modulates the timing of puberty in mice"],"prefix":"10.1136","volume":"43","author":[{"given":"R","family":"Jin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C A","family":"Hodges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M L","family":"Drumm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M R","family":"Palmert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2006,6,1]]},"reference":[{"key":"2025100511431019000_43.6.e29.1","first-page":"145","volume":"13","year":"2002","journal-title":"Adolesc Med"},{"key":"2025100511431019000_43.6.e29.2","unstructured":"Welsh MJ, Tsui L, Boat TF, Beaudet AL. Cystic fibrosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic basis of inherited disease. 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