{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:09:28Z","timestamp":1790150968062,"version":"4.0.1"},"reference-count":39,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["R01 HD110500"],"award-info":[{"award-number":["R01 HD110500"]}],"id":[{"id":"https:\/\/ror.org\/04byxyr05","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Orphan Disease Center, Perelman School of Medicine, University of Pennsylvania","award":["MDBR-20-135-SRS"],"award-info":[{"award-number":["MDBR-20-135-SRS"]}],"id":[{"id":"https:\/\/ror.org\/00b30xv10","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Chan Zuckerberg Initiative","id":[{"id":"https:\/\/ror.org\/02qenvm24","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institutes of Health","award":["U42 OD010921"],"award-info":[{"award-number":["U42 OD010921"]}]},{"name":"National Institutes of Health","award":["U54 OD030187"],"award-info":[{"award-number":["U54 OD030187"]}]},{"name":"National Institutes of Health","award":["U54 OD020351"],"award-info":[{"award-number":["U54 OD020351"]}]},{"name":"Snyder-Robinson Foundation"},{"name":"Johns Hopkins University","id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Snyder\u2013Robinson syndrome (SRS) is a rare X-linked disorder, caused by pathogenic variants in spermine synthase (SMS), associated with spermine deficiency and excessive spermidine accumulation. Previously reported mouse models exhibited reduced birthrate and survival of affected males, greatly limiting their experimental utility. Here, we describe a new mouse model, carrying the clinically relevant Sms p.Gly56Ser (SmsG56S) allele, in which viable males are recovered at Mendelian ratios, enabling generation of adequately powered cohorts. Hemizygous males produced markedly reduced SMS protein across tissues, recreating the biochemical hallmark of SRS, an elevated spermidine:spermine ratio. SmsG56S\/Y males exhibited reduced body size, altered body composition, decreased locomotor and exploratory behaviors, and reduced seizure threshold, aligning with clinical features reported in patients with SRS. Serum low-density lipoprotein, high-density lipoprotein and cholesterol levels were reduced, while brain histology revealed modest region-specific astrocytic changes. Comprehensive polyamine profiling revealed tissue-specific biochemical disturbances, highlighting putrescine elevation in the brain and informing the development of translational strategies and windows for intervention. Overall, this improved model reproduces multiple key aspects of the human SRS phenotype and provides a robust platform for mechanistic studies and preclinical evaluation of therapies.<\/jats:p>","DOI":"10.1242\/dmm.052953","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T06:35:54Z","timestamp":1785479754000},"source":"Crossref","is-referenced-by-count":0,"title":["An improved\n                    <i>Sms<\/i>\n                    p.Gly56Ser model of Snyder\u2013Robinson syndrome reveals phenotypic parallels with clinical features"],"prefix":"10.1242","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8679-6414","authenticated-orcid":false,"given":"Tracy","family":"Murray Stewart","sequence":"first","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine 1 , Baltimore, MD 21287 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh","family":"Tata","sequence":"additional","affiliation":[{"name":"Rare Disease Translational Center, The Jackson Laboratory 2 , Bar Harbor, ME 04609 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6315-7279","authenticated-orcid":false,"given":"Pierre-Alexandre","family":"Piec","sequence":"additional","affiliation":[{"name":"Rare Disease Translational Center, The Jackson Laboratory 2 , Bar Harbor, ME 04609 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4383-9522","authenticated-orcid":false,"given":"Jackson R.","family":"Foley","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine 1 , Baltimore, MD 21287 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teri","family":"Koerner","sequence":"additional","affiliation":[{"name":"Snyder-Robinson Foundation 3 , McLean, VA 22101 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Jo","family":"Kutler","sequence":"additional","affiliation":[{"name":"Snyder-Robinson Foundation 3 , McLean, VA 22101 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony E.","family":"Pegg","sequence":"additional","affiliation":[{"name":"Pennsylvania State University College of Medicine 4 Department of Cell and Biological Systems , , Hershey, PA 17033 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7770-1943","authenticated-orcid":false,"given":"Charles E.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Snyder-Robinson Foundation 3 , McLean, VA 22101 ,","place":["USA"]},{"name":"International Center for Polyamine Disorders 5 , Department of Pediatrics and Human Development , , Grand Rapids, MI 49503 ,","place":["USA"]},{"name":"College of Human Medicine, Michigan State University 5 , Department of Pediatrics and Human Development , , Grand Rapids, MI 49503 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Robert A.","family":"Casero","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine 1 , Baltimore, MD 21287 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aamir","family":"Zuberi","sequence":"additional","affiliation":[{"name":"Rare Disease Translational Center, The Jackson Laboratory 2 , Bar Harbor, ME 04609 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathleen","family":"Lutz","sequence":"additional","affiliation":[{"name":"Rare Disease Translational Center, The Jackson Laboratory 2 , Bar Harbor, ME 04609 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0160-6528","authenticated-orcid":false,"given":"Maximiliano","family":"Presa","sequence":"additional","affiliation":[{"name":"Rare Disease Translational Center, The Jackson Laboratory 2 , Bar Harbor, ME 04609 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"2026092303445098600_DMM052953C1","doi-asserted-by":"publisher","first-page":"dmm050639","DOI":"10.1242\/dmm.050639","article-title":"Impaired polyamine metabolism causes behavioral and neuroanatomical defects in a mouse model of Snyder-Robinson syndrome","volume":"17","author":"Akinyele","year":"2024","journal-title":"Dis. 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