{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T11:37:45Z","timestamp":1693222665300},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T00:00:00Z","timestamp":1571875200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T00:00:00Z","timestamp":1571875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Vet Res"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n              <jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Glucocorticoids, among the most widely utilized drugs in veterinary medicine, are employed to treat a wide variety of diseases; however, their use often induces adverse events in dogs. The efficacy of glucocorticoids usually depends on dosage, although differences in sensitivity to glucocorticoids in individual animals have been reported. Glucocorticoids bind to the cytoplasmic glucocorticoid receptor (GR), which is expressed in almost all cells. These receptors are key factors in determining individual sensitivity to glucocorticoids. This study examined individual differences in glucocorticoid sensitivity in dogs, focusing on reactivity of the GR to prednisolone.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We first molecularly cloned the <jats:italic>GR<\/jats:italic> gene from a healthy dog. We discovered a mutant <jats:italic>GR<\/jats:italic> in a dog suspected to have iatrogenic Cushing syndrome. The mutant <jats:italic>GR<\/jats:italic> had extra nucleotides between exons 6 and 7, resulting in a truncated form of GR that was 98 amino acids shorter than the wild-type dog GR. The truncated GR exhibited very low reactivity to prednisolone, irrespective of concentration.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We have identified the truncated form of canine GR in a dog with iatrogenic Cushing syndrome. This truncated form showed the very less sensitivity to glucocorticoid <jats:italic>in vitro<\/jats:italic>, unfortunately, we could not elucidate its clinical significance. However, our data is a first report about the function of canine GR, and will facilitate the analysis of canine glucocorticoid sensitivity.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12917-019-2129-9","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T12:17:37Z","timestamp":1572005857000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional characterization of canine wild type glucocorticoid receptor and an insertional mutation in a dog"],"prefix":"10.1186","volume":"15","author":[{"given":"Kosei","family":"Yamanaka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaru","family":"Okuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Mizuno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,10,24]]},"reference":[{"key":"2129_CR1","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1210\/jc.2008-0040","volume":"93","author":"E Charmandari","year":"2008","unstructured":"Charmandari E, Kino T, Ichijo T, Chrousos GP. Generalized glucocorticoid resistance: clinical aspects, molecular mechanisms, and implications of a rare genetic disorder. J Clin Endocrinol Metab Endocrine Soc. 2008;93:1563\u201372.","journal-title":"J Clin Endocrinol Metab Endocrine Soc"},{"key":"2129_CR2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.jss.2012.12.027","volume":"180","author":"AC Baker","year":"2013","unstructured":"Baker AC, Chew VW, Green TL, Tung K, Lim D, Cho K, et al. Single nucleotide polymorphisms and type of steroid impact the functional response of the human glucocorticoid receptor. J Surg Res. 2013;180:27\u201334.","journal-title":"J Surg Res"},{"key":"2129_CR3","doi-asserted-by":"publisher","first-page":"E790","DOI":"10.1210\/jc.2012-3549","volume":"98","author":"ML Roberts","year":"2013","unstructured":"Roberts ML, Kino T, Nicolaides NC, Hurt DE, Katsantoni E, Sertedaki A, et al. A novel point mutation in the DNA-binding domain (DBD) of the human glucocorticoid receptor causes primary generalized glucocorticoid resistance by disrupting the hydrophobic structure of its DBD. J Clin Endocrinol Metab. 2013;98:E790\u20135.","journal-title":"J Clin Endocrinol Metab"},{"key":"2129_CR4","first-page":"431","volume":"8","author":"MC Keightley","year":"1994","unstructured":"Keightley MC, Fuller PJ. Unique sequences in the Guinea pig glucocorticoid receptor induce constitutive transactivation and decrease steroid sensitivity. Mol Endocrinol. 1994;8:431\u20139.","journal-title":"Mol Endocrinol"},{"key":"2129_CR5","doi-asserted-by":"publisher","first-page":"E490","DOI":"10.1210\/jc.2010-0705","volume":"95","author":"P Trebble","year":"2010","unstructured":"Trebble P, Matthews L, Blaikley J, Wayte AWO, Black GCM, Wilton A, et al. Familial glucocorticoid resistance caused by a novel Frameshift glucocorticoid receptor mutation. J Clin Endocrinol Metab. 2010;95:E490\u20139.","journal-title":"J Clin Endocrinol Metab"},{"key":"2129_CR6","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1111\/j.1365-3164.2008.00717.x","volume":"19","author":"AD Lowe","year":"2008","unstructured":"Lowe AD, Campbell KL, Graves T. Glucocorticoids in the cat. Vet Dermatol. 2008;19:340\u20137.","journal-title":"Vet Dermatol"},{"key":"2129_CR7","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1016\/j.steroids.2012.05.007","volume":"77","author":"N Yang","year":"2012","unstructured":"Yang N, Ray DW, Matthews LC. Current concepts in glucocorticoid resistance. Steroids. 2012;77:1041\u20139.","journal-title":"Steroids."},{"key":"2129_CR8","doi-asserted-by":"publisher","first-page":"3947","DOI":"10.1128\/MCB.17.7.3947","volume":"17","author":"MD Krstic","year":"1997","unstructured":"Krstic MD, Rogatsky I, Yamamoto KR, Garabedian MJ. Mitogen-activated and cyclin-dependent protein kinases selectively and differentially modulate transcriptional enhancement by the glucocorticoid receptor. Mol Cell Biol. 1997;17:3947\u201354.","journal-title":"Mol Cell Biol"},{"key":"2129_CR9","doi-asserted-by":"publisher","first-page":"10762","DOI":"10.1073\/pnas.0805139105","volume":"105","author":"N Dephoure","year":"2008","unstructured":"Dephoure N, Zhou C, Vill\u00e9n J, Beausoleil SA, Bakalarski CE, Elledge SJ, et al. A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008;105:10762\u20137.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2129_CR10","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1677\/joe.1.06799","volume":"190","author":"H Garside","year":"2006","unstructured":"Garside H, Waters C, Berry A, Rice L, Ardley HC, White A, et al. UbcH7 interacts with the glucocorticoid receptor and mediates receptor autoregulation. J Endocrinol. 2006;190:621\u20139.","journal-title":"J Endocrinol"},{"key":"2129_CR11","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1210\/er.2009-0013","volume":"30","author":"IME Beck","year":"2009","unstructured":"Beck IME, Vanden Berghe W, Vermeulen L, Yamamoto KR, Haegeman G, De Bosscher K. Crosstalk in inflammation: the interplay of glucocorticoid receptor-based mechanisms and kinases and phosphatases. Endocr Rev. 2009;30:830\u201382.","journal-title":"Endocr Rev"},{"key":"2129_CR12","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1084\/jem.20050466","volume":"203","author":"K Ito","year":"2006","unstructured":"Ito K, Yamamura S, Essilfie-Quaye S, Cosio B, Ito M, Barnes PJ, et al. Histone deacetylase 2-mediated deacetylation of the glucocorticoid receptor enables NF-kappaB suppression. J Exp Med. 2006;203:7\u201313.","journal-title":"J Exp Med"},{"key":"2129_CR13","first-page":"2292s","volume":"49","author":"SM Hollenberg","year":"1989","unstructured":"Hollenberg SM, Giguere V, Evans RM. Identification of two regions of the human glucocorticoid receptor hormone binding domain that block activation. Cancer Res. 1989;49:2292s\u20134s.","journal-title":"Cancer Res"},{"key":"2129_CR14","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/0039-128X(94)00014-4","volume":"60","author":"MC Keightley","year":"1995","unstructured":"Keightley MC, Fuller PJ. Cortisol resistance and the Guinea pig glucocorticoid receptor. Steroids. 1995;60:87\u201392.","journal-title":"Steroids."},{"key":"2129_CR15","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1111\/j.1749-6632.2002.tb04416.x","volume":"970","author":"T Kino","year":"2002","unstructured":"Kino T, Vottero A, Charmandari E, Chrousos GP. Familial\/sporadic glucocorticoid resistance syndrome and hypertension. Ann N Y Acad Sci. 2002;970:101\u201311.","journal-title":"Ann N Y Acad Sci"},{"key":"2129_CR16","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/S0303-7207(02)00280-0","volume":"197","author":"SWJ Lamberts","year":"2002","unstructured":"Lamberts SWJ. Glucocorticoid receptors and Cushing's disease. Mol Cell Endocrinol. 2002;197:69\u201372.","journal-title":"Mol Cell Endocrinol"},{"key":"2129_CR17","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/S0950-351X(05)80255-1","volume":"8","author":"K Arai","year":"1994","unstructured":"Arai K, Chrousos GP. Hormone-nuclear receptor interactions in health and disease. Glucocorticoid resistance. Baillieres Clin Endocrinol Metab. 1994;8:317\u201331.","journal-title":"Baillieres Clin Endocrinol Metab"}],"container-title":["BMC Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-019-2129-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12917-019-2129-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-019-2129-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T23:10:55Z","timestamp":1603408255000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcvetres.biomedcentral.com\/articles\/10.1186\/s12917-019-2129-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,24]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["2129"],"URL":"https:\/\/doi.org\/10.1186\/s12917-019-2129-9","relation":{},"ISSN":["1746-6148"],"issn-type":[{"value":"1746-6148","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,24]]},"assertion":[{"value":"15 April 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 October 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was approved by the ethics committee of Yamaguchi University Animal Medical Center. Informed consent for taking blood was verbally obtained from the owner and was filled in medical chart. The committee approved the verbal consent at that stage because the comprehensive prior consent arrangement was also taken with documents at the first visit.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"We obtained a written consent from the owner to use a dog\u2019s picture.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"363"}}