{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:45:33Z","timestamp":1783568733805,"version":"3.55.0"},"reference-count":57,"publisher":"The Endocrine Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,6,1]]},"abstract":"<jats:p>Pseudohypoparathyroidism type Ib (PHP-Ib) is characterized by hypocalcemia and hyperphosphatemia due to proximal renal tubular resistance to PTH but without evidence for Albright\u2019s hereditary osteodystrophy. The disorder is paternally imprinted and affected individuals, but not unaffected carriers, show loss of GNAS exon A\/B methylation, a differentially methylated region upstream of the exons encoding Gs\u03b1. Affected individuals of numerous unrelated kindreds with an autosomal dominant form of PHP-Ib (AD-PHP-Ib) have an identical 3-kb microdeletion removing exons 4\u20136 of syntaxin-16 (STX16) (STX16del4\u20136), which is thought to disrupt a cis-acting element required for exon A\/B methylation. To explore the mechanisms underlying the regulation of exon A\/B methylation, we generated mice genetically altered to carry the equivalent of STX16del4\u20136 (Stx16\u03944\u20136). Although the human GNAS locus shows a similar organization as the murine Gnas ortholog and although the human and mouse STX16\/Stx16 regions show no major structural differences, no phenotypic or epigenotypic abnormalities were detected in mice with Stx16\u03944\u20136 on one or both parental alleles. Furthermore, calcium and PTH levels in Stx16\u03944\u20136 mice were indistinguishable from those in wild-type animals, indicating that ablation of the murine equivalent of human STX16del4\u20136 does not contribute to the development of PTH resistance. The identification of a novel intragenic transcript from within the STX16\/Stx16 locus in total RNA from kidneys of Stx16\u03944\u20136 mice and lymphoblastoid cell-derived RNA of a patient with AD-PHP-Ib raises the question whether this transcript contributes, if deleted or altered, to the development of AD-PHP-Ib in humans.<\/jats:p>","DOI":"10.1210\/en.2006-1298","type":"journal-article","created":{"date-parts":[[2007,2,23]],"date-time":"2007-02-23T12:14:34Z","timestamp":1172232874000},"page":"2925-2935","source":"Crossref","is-referenced-by-count":31,"title":["Lack of Gnas Epigenetic Changes and Pseudohypoparathyroidism Type Ib in Mice with Targeted Disruption of Syntaxin-16"],"prefix":"10.1210","volume":"148","author":[{"given":"Leopold F.","family":"Fro\u0308hlich","sequence":"first","affiliation":[{"name":"Endocrine Unit (L.F.F., M.B., D.O., H.A.-Z., H.J.), Department of Medicine and Massachusetts General Hospital for Children, Massachusetts General Hospital and Harvard Medical 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General Hospital and Harvard Medical School, Boston, Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Ju\u0308ppner","sequence":"first","affiliation":[{"name":"Endocrine Unit (L.F.F., M.B., D.O., H.A.-Z., H.J.), Department of Medicine and Massachusetts General Hospital for Children, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114"},{"name":"Pediatric Nephrology Unit (H.J.), Department of Medicine and Massachusetts General Hospital for Children, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613034525900_R1","doi-asserted-by":"crossref","first-page":"10038","DOI":"10.1073\/pnas.95.17.10038","article-title":"The human GNAS1 gene is imprinted and encodes distinct paternally and biallelically expressed G 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