{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,4]],"date-time":"2024-08-04T17:55:55Z","timestamp":1722794155504},"reference-count":58,"publisher":"The Endocrine Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,2,1]]},"abstract":"<jats:p>Combined pituitary hormone deficiency (CPHD) diseases result in severe outcomes for patients including short stature, developmental delays, and reproductive deficiencies. Little is known about their etiology, especially the developmental profiles and the influences of genetic background on disease progression. Animal models for CPHD provide valuable tools to investigate disease mechanisms and inform diagnostic and treatment protocols. Here we examined hormone production during pituitary development and the influence of genetic background on phenotypic severity in the Lhx3W227ter\/W227ter mouse model. Lhx3W227ter\/W227ter embryos have deficiencies of ACTH, \u03b1-glycoprotein subunit, GH, PRL, TSH\u03b2, and LH\u03b2 during prenatal development. Furthermore, mutant mice have significant reduction in the critical pituitary transcriptional activator-1 (PIT1). Through breeding, the Lhx3W227ter\/W227ter genotype was placed onto the 129\/Sv and C57BL\/6 backgrounds. Intriguingly, the genetic background significantly affected viability: whereas Lhx3W227ter\/W227ter animals were found in the expected frequencies in C57BL\/6, homozygous animals were not viable in the 129\/Sv genetic environment. The hormone marker and PIT1 reductions observed in Lhx3W227ter\/W227ter mice on a mixed background were also seen in the separate strains but in some cases were more severe in 129\/Sv. To further characterize the molecular changes in diseased mice, we conducted a quantitative proteomic analysis of pituitary proteins. This showed significantly lower levels of PRL, pro-opiomelanocortin (ACTH), and \u03b1-glycoprotein subunit proteins in Lhx3W227ter\/W227ter mice. Together, these data show that hormone deficiency disease is apparent in early prenatal stages in this CPHD model system. Furthermore, as is noted in human disease, genetic background significantly impacts the phenotypic outcome of these monogenic endocrine diseases.<\/jats:p>","DOI":"10.1210\/en.2012-1790","type":"journal-article","created":{"date-parts":[[2013,1,4]],"date-time":"2013-01-04T07:07:04Z","timestamp":1357283224000},"page":"738-748","source":"Crossref","is-referenced-by-count":7,"title":["Developmental Analysis and Influence of Genetic Background on the Lhx3 W227ter Mouse Model of Combined Pituitary Hormone Deficiency Disease"],"prefix":"10.1210","volume":"154","author":[{"given":"Kelly L.","family":"Prince","sequence":"first","affiliation":[{"name":"Departments of Cellular and Integrative Physiology (K.L.P., S.C.C., X.L., F.A.W., S.J.R.),Indiana University-Purdue University, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie C.","family":"Colvin","sequence":"first","affiliation":[{"name":"Departments of Cellular and Integrative Physiology (K.L.P., S.C.C., X.L., F.A.W., S.J.R.),Indiana University-Purdue University, Indianapolis, Indiana 46202"},{"name":"Indiana University School of Medicine, and Department of Biology (S.C.C., S.J.R.), Indiana University-Purdue University, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soyoung","family":"Park","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Biology (S.P., S.J.R.),Indiana University-Purdue University, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianyin","family":"Lai","sequence":"first","affiliation":[{"name":"Departments of Cellular and Integrative Physiology (K.L.P., S.C.C., X.L., F.A.W., S.J.R.),Indiana University-Purdue University, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank A.","family":"Witzmann","sequence":"first","affiliation":[{"name":"Departments of Cellular and Integrative Physiology (K.L.P., S.C.C., X.L., F.A.W., S.J.R.),Indiana University-Purdue University, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon J.","family":"Rhodes","sequence":"first","affiliation":[{"name":"Departments of Cellular and Integrative Physiology (K.L.P., S.C.C., X.L., F.A.W., S.J.R.),Indiana University-Purdue University, Indianapolis, Indiana 46202"},{"name":"Biochemistry and Molecular Biology (S.P., S.J.R.),Indiana University-Purdue University, Indianapolis, Indiana 46202"},{"name":"Indiana University School of Medicine, and Department of Biology (S.C.C., S.J.R.), Indiana University-Purdue University, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2013,1,3]]},"reference":[{"key":"2020071612390528500_B1","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1210\/er.2009-0008","article-title":"Genetic regulation of pituitary gland development in human and 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