{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T16:40:27Z","timestamp":1782837627010,"version":"3.54.5"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,1,4]]},"abstract":"<jats:p>\n                    The etiology of most pediatric hormone deficiency diseases is poorly understood. Children with combined pituitary hormone deficiency (CPHD) have insufficient levels of multiple anterior pituitary hormones causing short stature, metabolic disease, pubertal failure, and often have associated nervous system symptoms. Mutations in developmental regulatory genes required for the specification of the hormone-secreting cell types of the pituitary gland underlie severe forms of CPHD. To better understand these diseases, we have created a unique mouse model of CPHD with a targeted knockin mutation (\n                    <jats:italic>Lhx3<\/jats:italic>\n                    W227ter), which is a model for the human\n                    <jats:italic>LHX3<\/jats:italic>\n                    W224ter disease. The\n                    <jats:italic>LHX3<\/jats:italic>\n                    gene encodes a LIM-homeodomain transcription factor, which has essential roles in pituitary and nervous system development in mammals. The introduced premature termination codon results in deletion of the carboxyl terminal region of the LHX3 protein, which is critical for pituitary gene activation. Mice that lack all LHX3 function do not survive beyond birth. By contrast, the homozygous\n                    <jats:italic>Lhx3<\/jats:italic>\n                    W227ter mice survive, but display marked dwarfism, thyroid disease, and female infertility. Importantly, the\n                    <jats:italic>Lhx3<\/jats:italic>\n                    W227ter mice have no apparent nervous system deficits. The\n                    <jats:italic>Lhx3<\/jats:italic>\n                    W227ter mouse model provides a unique array of hormone deficits and facilitates experimental approaches that are not feasible with human patients. These experiments demonstrate that the carboxyl terminus of the LHX3 transcription factor is not required for viability. More broadly, this study reveals that the in vivo actions of a transcription factor in different tissues are molecularly separable.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1009501108","type":"journal-article","created":{"date-parts":[[2010,12,13]],"date-time":"2010-12-13T23:49:21Z","timestamp":1292284161000},"page":"173-178","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":20,"title":["Model of pediatric pituitary hormone deficiency separates the endocrine and neural functions of the LHX3 transcription factor in vivo"],"prefix":"10.1073","volume":"108","author":[{"given":"Stephanie C.","family":"Colvin","sequence":"first","affiliation":[{"name":"Departments of aCellular and Integrative Physiology and"},{"name":"Department of Biology, Indiana University\u2013Purdue University, Indianapolis, IN 46202; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raleigh E.","family":"Malik","sequence":"additional","affiliation":[{"name":"Departments of aCellular and Integrative Physiology and"},{"name":"Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron D.","family":"Showalter","sequence":"additional","affiliation":[{"name":"Endocrine Discovery, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle W.","family":"Sloop","sequence":"additional","affiliation":[{"name":"Endocrine Discovery, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J.","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Departments of aCellular and Integrative Physiology and"},{"name":"Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202;"},{"name":"Department of Biology, Indiana University\u2013Purdue University, Indianapolis, IN 46202; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,12,13]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00006.2006"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2009-0008"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81704-3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5264.1004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5344.1809"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.7.2720"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103888200"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.13.12.0395"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0598"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-1566"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0184"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00823-1"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-2360"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/76041"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn114"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2177"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0325"},{"key":"e_1_3_3_18_2","first-page":"283","article-title":"LHX3 and LHX4 transcription factors in pituitary development and disease","volume":"6","author":"Colvin SC","year":"2009","unstructured":"SC Colvin, RD Mullen, RW Pfaeffle, SJ Rhodes, LHX3 and LHX4 transcription factors in pituitary development and disease. 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