{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:44:14Z","timestamp":1791182654560,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["HL140025"],"award-info":[{"award-number":["HL140025"]}]},{"name":"NIH","award":["R24 GM082910"],"award-info":[{"award-number":["R24 GM082910"]}]},{"name":"Laboklin GmbH &amp; Co. KG","award":["HL140025"],"award-info":[{"award-number":["HL140025"]}]},{"name":"Laboklin GmbH &amp; Co. KG","award":["R24 GM082910"],"award-info":[{"award-number":["R24 GM082910"]}]},{"name":"Cornell Veterinary Biobank","award":["HL140025"],"award-info":[{"award-number":["HL140025"]}]},{"name":"Cornell Veterinary Biobank","award":["R24 GM082910"],"award-info":[{"award-number":["R24 GM082910"]}]},{"name":"College of Veterinary Medicine, Cornell University","award":["HL140025"],"award-info":[{"award-number":["HL140025"]}]},{"name":"College of Veterinary Medicine, Cornell University","award":["R24 GM082910"],"award-info":[{"award-number":["R24 GM082910"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Hereditary factor XI (FXI) deficiency is characterized as an autosomal mild to moderate coagulopathy in humans and domestic animals. Coagulation testing revealed FXI deficiency in a core family of Maine Coon cats (MCCs) in the United States. Factor XI-deficient MCCs were homozygous for a guanine to adenine transition resulting in a methionine substitution for the highly conserved valine-516 in the FXI catalytic domain. Immunoblots detected FXI of normal size and quantity in plasmas of MCCs homozygous for V516M. Some FXI-deficient MCCs experienced excessive post-operative\/traumatic bleeding. Screening of 263 MCCs in Europe revealed a mutant allele frequency of 0.232 (23.2%). However, V516M was not found among 100 cats of other breeds. Recombinant feline FXI-M516 (fFXI-M516) expressed ~4% of the activity of wild-type fFXI-V516 in plasma clotting assays. Furthermore, fFXIa-M516 cleaved the chromogenic substrate S-2366 with ~4.3-fold lower catalytic efficacy (kcat\/Km) than fFXIa-V516, supporting a conformational alteration of the protease active site. The rate of FIX activation by fFXIa-M516 was reduced &gt;3-fold compared with fFXIa-V516. The common missense variant FXI-V516M causes a cross-reactive material positive FXI deficiency in MCCs that is associated with mild-moderate bleeding tendencies. Given the prevalence of the variant in MCCs, genotyping is recommended prior to invasive procedures or breeding.<\/jats:p>","DOI":"10.3390\/genes13050792","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T12:06:01Z","timestamp":1651147561000},"page":"792","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Common Missense Variant Causing Factor XI Deficiency and Increased Bleeding Tendency in Maine Coon Cats"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4138-5782","authenticated-orcid":false,"given":"Henrike","family":"Kuder","sequence":"first","affiliation":[{"name":"Vetsuisse Faculty, University of Z\u00fcrich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland"},{"name":"Laboklin GmbH & Co. KG (Labogen), Steubenstrasse 4, D-97688 Bad Kissingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Kent","family":"Dickeson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, 1301 Medical Center Dr, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjory B.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Comparative Coagulation Laboratory, Cornell University, 240 Farrier Road, Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1547-0713","authenticated-orcid":false,"given":"Alexandra","family":"Kehl","sequence":"additional","affiliation":[{"name":"Laboklin GmbH & Co. KG (Labogen), Steubenstrasse 4, D-97688 Bad Kissingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Laboklin GmbH & Co. KG (Labogen), Steubenstrasse 4, D-97688 Bad Kissingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gailani","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, 1301 Medical Center Dr, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-4107","authenticated-orcid":false,"given":"Urs","family":"Giger","sequence":"additional","affiliation":[{"name":"Vetsuisse Faculty, University of Z\u00fcrich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6135","DOI":"10.1182\/bloodadvances.2020002456","article-title":"The Evolution of Factor XI and the Kallikrein-Kinin System","volume":"4","author":"Ponczek","year":"2020","journal-title":"Blood Adv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.thromres.2017.10.008","article-title":"An Update on Factor XI Structure and Function","volume":"161","author":"Mohammed","year":"2018","journal-title":"Thromb. 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VS"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/5\/792\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:03:17Z","timestamp":1760137397000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/5\/792"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,28]]},"references-count":54,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["genes13050792"],"URL":"https:\/\/doi.org\/10.3390\/genes13050792","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,28]]}}}