{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:53:53Z","timestamp":1790009633328,"version":"4.0.1"},"reference-count":58,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,11,1]]},"abstract":"<jats:p>Albright hereditary osteodystrophy is caused by heterozygous inactivating mutations in GNAS, a gene that encodes not only the \u03b1-chain of Gs (G\u03b1s), but also NESP55 and XL\u03b1s through use of alternative first exons. Patients with GNAS mutations on maternally inherited alleles are resistant to multiple hormones such as PTH, TSH, LH\/FSH, GHRH, and glucagon, whose receptors are coupled to Gs. This variant of Albright hereditary osteodystrophy is termed pseudohypoparathyroidism type 1a and is due to presumed tissue-specific paternal imprinting of G\u03b1s. Previous studies have shown that mice heterozygous for a targeted disruption of exon 2 of Gnas, the murine homolog of GNAS, showed unique phenotypes dependent on the parent of origin of the mutated allele. However, hormone resistance occurred only when the disrupted gene was maternally inherited. Because disruption of exon 2 is predicted to inactivate G\u03b1s as well as NESP55 and XL\u03b1s, we created transgenic mice with disruption of exon 1 to investigate the effects of isolated loss of G\u03b1s. Heterozygous mice that inherited the disruption maternally (\u2212m\/+) exhibited PTH and TSH resistance, whereas those with paternal inheritance (+\/\u2212p) had normal hormone responsiveness. Heterozygous mice were shorter and, when the disrupted allele was inherited maternally, weighed more than wild-type littermates. G\u03b1s protein and mRNA expression was consistent with paternal imprinting in the renal cortex and thyroid, but there was no imprinting in renal medulla, heart, or adipose. These findings confirm the tissue-specific paternal imprinting of GNAS and demonstrate that G\u03b1s deficiency alone is sufficient to account for the hormone resistance of pseudohypoparathyroidism type 1a.<\/jats:p>","DOI":"10.1210\/en.2005-0681","type":"journal-article","created":{"date-parts":[[2005,8,12]],"date-time":"2005-08-12T01:48:28Z","timestamp":1123811308000},"page":"4697-4709","source":"Crossref","is-referenced-by-count":109,"title":["A Mouse Model of Albright Hereditary Osteodystrophy Generated by Targeted Disruption of Exon 1 of the Gnas Gene"],"prefix":"10.1210","volume":"146","author":[{"given":"Emily L.","family":"Germain-Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Schwindinger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet L.","family":"Crane","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rediet","family":"Zewdu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry S.","family":"Zweifel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Wand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Huso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoyasu","family":"Saji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Ringel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Levine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612383866000_R1","first-page":"1137","author":"Levine","year":"2002"},{"key":"2020071612383866000_R2","first-page":"675","article-title":"Endocrine manifestations of stimulatory G protein \u03b1-subunit mutations and the role of genomic imprinting.","volume":"22","author":"Weinstein","year":"2001","journal-title":"Endocr Rev"},{"key":"2020071612383866000_R3","first-page":"922","article-title":"Pseudohypoparathyroidism: an example of \u201cSeabright-Bantam syndrome.\u201d","volume":"30","author":"Albright","year":"1942","journal-title":"Endocrinology"},{"key":"2020071612383866000_R4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1136\/jmg.30.2.101","article-title":"Imprinting in Albright\u2019s hereditary osteodystrophy.","volume":"30","author":"Davies","year":"1993","journal-title":"J Med Genet"},{"key":"2020071612383866000_R5","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1210\/jcem-63-6-1354","article-title":"Responses to glucagon infusion in pseudohypoparathyroidism.","volume":"63","author":"Brickman","year":"1986","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612383866000_R6","doi-asserted-by":"crossref","first-page":"4059","DOI":"10.1210\/jc.2003-030028","article-title":"Growth hormone deficiency in pseudohypoparathyroidism type 1a: another manifestation of multihormone resistance.","volume":"88","author":"Germain-Lee","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612383866000_R7","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/0002-9343(83)91008-2","article-title":"Resistance to multiple hormones in patients with pseudohypoparathyroidism. 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