{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:34:24Z","timestamp":1791196464212,"version":"4.1.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,7,21]]},"abstract":"<jats:p>\n                    Albright hereditary osteodystrophy (AHO), an autosomal dominant disorder characterized by short stature, obesity, and skeletal defects, is associated with heterozygous inactivating mutations of\n                    <jats:italic>GNAS1<\/jats:italic>\n                    , the gene encoding the heterotrimeric G protein \u03b1-subunit (G\n                    <jats:sub>s<\/jats:sub>\n                    \u03b1) that couples multiple receptors to the stimulation of adenylyl cyclase. It has remained unclear why only some AHO patients present with multihormone resistance and why AHO patients demonstrate resistance to some hormones [e.g., parathyroid hormone (PTH)] but not to others (e.g., vasopressin), even though all activate adenylyl cyclase. We generated mice with a null allele of the mouse homolog\n                    <jats:italic>Gnas.<\/jats:italic>\n                    Homozygous G\n                    <jats:sub>s<\/jats:sub>\n                    deficiency is embryonically lethal. Heterozygotes with maternal (m\u2212\/+) and paternal (+\/p\u2212) inheritance of the\n                    <jats:italic>Gnas<\/jats:italic>\n                    null allele have distinct phenotypes, suggesting that\n                    <jats:italic>Gnas<\/jats:italic>\n                    is an imprinted gene. PTH resistance is present in m\u2212\/+, but not +\/p\u2212, mice. G\n                    <jats:sub>s<\/jats:sub>\n                    \u03b1 expression in the renal cortex (the site of PTH action) is markedly reduced in m\u2212\/+ but not in +\/p\u2212 mice, demonstrating that the\n                    <jats:italic>Gnas<\/jats:italic>\n                    paternal allele is imprinted in this tissue.\n                    <jats:italic>Gnas<\/jats:italic>\n                    is also imprinted in brown and white adipose tissue. The maximal physiological response to vasopressin (urinary concentrating ability) is normal in both m\u2212\/+ and +\/p\u2212 mice and\n                    <jats:italic>Gnas<\/jats:italic>\n                    is not imprinted in the renal inner medulla (the site of vasopressin action). Tissue-specific imprinting of\n                    <jats:italic>Gnas<\/jats:italic>\n                    is likely the mechanism for variable and tissue-specific hormone resistance in these mice and a similar mechanism might explain the variable phenotype in AHO.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.15.8715","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:42:40Z","timestamp":1027680160000},"page":"8715-8720","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":348,"title":["Variable and tissue-specific hormone resistance in heterotrimeric G\n                    <sub>s<\/sub>\n                    protein \u03b1-subunit (G\n                    <sub>s<\/sub>\n                    \u03b1) knockout mice is due to tissue-specific imprinting of the G\n                    <sub>s<\/sub>\n                    \u03b1 gene"],"prefix":"10.1073","volume":"95","author":[{"given":"Shuhua","family":"Yu","sequence":"first","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Laboratory of Mammalian Genes and Development and Developmental Endocrinology Branch, National Institute of Child Health and Human Development, and Veterinary Research Program, National Center for Research Resources, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawen","family":"Yu","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Laboratory of Mammalian Genes and Development and Developmental Endocrinology Branch, National Institute of Child Health and Human Development, and Veterinary Research Program, National Center for Research Resources, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Lee","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Laboratory of Mammalian Genes and Development and Developmental Endocrinology Branch, National Institute of Child Health and Human Development, and Veterinary Research Program, National Center for Research Resources, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Eckhaus","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Laboratory of Mammalian Genes and Development and Developmental Endocrinology Branch, National Institute of Child Health and Human Development, and Veterinary Research Program, National Center for Research Resources, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy","family":"Lee","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Laboratory of Mammalian Genes and Development and Developmental Endocrinology Branch, National Institute of Child Health and Human Development, and Veterinary Research Program, National Center for Research Resources, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zakia","family":"Corria","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Laboratory of Mammalian Genes and Development and Developmental Endocrinology Branch, National Institute of Child Health and Human Development, and Veterinary Research Program, National Center for Research Resources, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Accili","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Laboratory of Mammalian Genes and Development and Developmental Endocrinology Branch, National Institute of Child Health and Human Development, and Veterinary Research Program, National Center for Research Resources, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiner","family":"Westphal","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Laboratory of Mammalian Genes and Development and Developmental Endocrinology Branch, National Institute of Child Health and Human Development, and Veterinary Research Program, National Center for Research Resources, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee S.","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Laboratory of Mammalian Genes and Development and Developmental Endocrinology Branch, National Institute of Child Health and Human Development, and Veterinary Research Program, National Center for Research Resources, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,7,21]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-13-3-536"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(91)90377-Q"},{"key":"e_1_3_3_3_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/978-1-4612-1802-9_2","volume-title":"G Proteins, Receptors, and Disease","author":"Weinstein L S","year":"1998","unstructured":"L S Weinstein G Proteins, Receptors, and Disease, ed A M Spiegel (Humana, Totowa, NJ), pp. 23\u201356 (1998)."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199005173222010"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.31.1.493"},{"key":"e_1_3_3_6_2","first-page":"64","volume":"87","author":"Beechey C V","year":"1990","unstructured":"C V Beechey, B M Cattanach, A G Searle Mouse Genome 87, 64\u201365 (1990).","journal-title":"Mouse Genome"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/315496a0"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0016672300032316"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0016672300033103"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1995.1192"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.30.2.101"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.31.8.607"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1996.0463"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.31.1.84"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90499-O"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0196-106"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.26.12564"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.21.8287"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.13.7.3990-3998.1993"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.13.4438"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.1825"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.10.5403"},{"key":"e_1_3_3_23_2","first-page":"F663","volume":"269","author":"Ecelbarger C A","year":"1995","unstructured":"C A Ecelbarger, J Terris, G Frindt, M Echevarria, D Marples, S Nielson, M A Knepper Am J Physiol 269, F663\u2013F672 (1995).","journal-title":"Am J Physiol"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(89)80622-2"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47929-X"},{"key":"e_1_3_3_26_2","first-page":"266","volume-title":"Handbook of Endocrine Research Techniques","author":"Bondy C A","year":"1993","unstructured":"C A Bondy, J Zhou, W H Lee Handbook of Endocrine Research Techniques, eds F de Pablo, C G Scanes (Academic, New York), pp. 266\u2013288 (1993)."},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(87)80486-6"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.274.1.F129"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.7.2081"},{"key":"e_1_3_3_30_2","doi-asserted-by":"crossref","unstructured":"Cattanach B. M. (1986) J. Embryol. Exp. Morph. 97 Suppl. 137\u2013150.","DOI":"10.1242\/dev.97.Supplement.137"},{"key":"e_1_3_3_31_2","doi-asserted-by":"crossref","unstructured":"Cattanach B. M. & Beechey C. V. (1990) Development (Cambridge U.K.) Suppl. 63\u201372.","DOI":"10.1242\/dev.108.Supplement.63"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-62-3-497"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(83)91008-2"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-63-6-1354"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-56-6-1323"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-61-2-382"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-62-1-221"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1997.8681"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0394-305"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90513-X"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0394-310"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0997-75"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/8756-3282(93)90204-N"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199112123252403"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.95.15.8715","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T16:33:02Z","timestamp":1649867582000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.95.15.8715"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,7,21]]},"references-count":44,"journal-issue":{"issue":"15","published-print":{"date-parts":[[1998,7,21]]}},"alternative-id":["10.1073\/pnas.95.15.8715"],"URL":"https:\/\/doi.org\/10.1073\/pnas.95.15.8715","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,7,21]]},"assertion":[{"value":"1998-02-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-06-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-07-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}