{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:44:54Z","timestamp":1787237094927,"version":"build-2736575974"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Mouse Animal Production Service"},{"name":"Centre of Molecular Medicine and Therapeutics"},{"name":"Rare Diseases: Models & Mechanisms Network","award":["# 27R21814"],"award-info":[{"award-number":["# 27R21814"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"British Columbia Children\u2019s Hospital Research Institute"},{"name":"Ministry of Higher Education, Oman, and Al Awael Overseas Company"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disease caused by mutations in the ALDH7A1 gene leading to blockade of the lysine catabolism pathway. PDE is characterized by recurrent seizures that are resistant to conventional anticonvulsant treatment but are well-controlled by pyridoxine (PN). Most PDE patients also suffer from neurodevelopmental deficits despite adequate seizure control with PN. To investigate potential pathophysiological mechanisms associated with ALDH7A1 deficiency, we generated a transgenic mouse strain with constitutive genetic ablation of Aldh7a1. We undertook extensive biochemical characterization of Aldh7a1-KO mice consuming a low lysine\/high PN diet. Results showed that KO mice accumulated high concentrations of upstream lysine metabolites including \u22061-piperideine-6-carboxylic acid (P6C), \u03b1-aminoadipic semialdehyde (\u03b1-AASA) and pipecolic acid both in brain and liver tissues, similar to the biochemical picture in ALDH7A1-deficient patients. We also observed preliminary evidence of a widely deranged amino acid profile and increased levels of methionine sulfoxide, an oxidative stress biomarker, in the brains of KO mice, suggesting that increased oxidative stress may be a novel pathobiochemical mechanism in ALDH7A1 deficiency. KO mice lacked epileptic seizures when fed a low lysine\/high PN diet. Switching mice to a high lysine\/low PN diet led to vigorous seizures and a quick death in KO mice. Treatment with PN controlled seizures and improved survival of high-lysine\/low PN fed KO mice. This study expands the spectrum of biochemical abnormalities that may be associated with ALDH7A1 deficiency and provides a proof-of-concept for the utility of the model to study PDE pathophysiology and to test new therapeutics.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa202","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T15:19:15Z","timestamp":1600442355000},"page":"3266-3284","source":"Crossref","is-referenced-by-count":39,"title":["A novel mouse model for pyridoxine-dependent epilepsy due to antiquitin deficiency"],"prefix":"10.1093","volume":"29","author":[{"given":"Hilal H","family":"Al-Shekaili","sequence":"first","affiliation":[{"name":"British Columbia Children\u2019s Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terri L","family":"Petkau","sequence":"additional","affiliation":[{"name":"Centre for Molecular 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Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Horvath","sequence":"additional","affiliation":[{"name":"Division of Biochemical Diseases, Department of Pediatrics, University of British Columbia and BC Children\u2019s Hospital, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Ross","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M","family":"Simpson","sequence":"additional","affiliation":[{"name":"British Columbia Children\u2019s Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada"},{"name":"Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M","family":"Friedman","sequence":"additional","affiliation":[{"name":"British Columbia Children\u2019s Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada"},{"name":"Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"van Karnebeek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Centre for Molecular Medicine and Therapeutics, BC Children\u2019s Research Institute, University of British Columbia, Vancouver, BC, Canada"},{"name":"Department of Pediatrics, Emma Children\u2019s Hospital, Amsterdam University Medical Centres, Amsterdam, The Netherlands"},{"name":"Department of Pediatrics, Amalia Children\u2019s Hospital, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blair R","family":"Leavitt","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"2020120619075338700_ref1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1002\/jimd.12045","article-title":"The genotypic spectrum of ALDH7A1 mutations resulting in pyridoxine dependent epilepsy: a common epileptic encephalopathy","volume":"42","author":"Coughlin","year":"2019","journal-title":"J. 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Basis Dis."},{"key":"2020120619075338700_ref26","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1007\/s00726-013-1590-1","article-title":"Lysine metabolism in mammalian brain: an update on the importance of recent discoveries","volume":"45","author":"Hallen","year":"2013","journal-title":"Amino Acids"},{"key":"2020120619075338700_ref27","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1023\/A:1006906505745","article-title":"Identification of L-amino acid\/L-lysine alpha-amino oxidase in mouse brain","volume":"197","author":"Murthy","year":"1999","journal-title":"Mol. Cell. Biochem."},{"key":"2020120619075338700_ref28","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/brain\/awq269","article-title":"Therapeutic modulation of cerebral L-lysine metabolism in a mouse model for glutaric aciduria type I","volume":"134","author":"Sauer","year":"2011","journal-title":"Brain"},{"key":"2020120619075338700_ref29","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0165-3806(85)90169-5","article-title":"Pipecolic acid levels and transport in developing mouse brain","volume":"354","author":"Kim","year":"1985","journal-title":"Brain Res."},{"key":"2020120619075338700_ref30","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/0167-4838(93)90108-4","article-title":"L-pipecolic acid oxidation in rat: subcellular localization and developmental study","volume":"1164","author":"Rao","year":"1993","journal-title":"Biochim. Biophys. Acta"},{"key":"2020120619075338700_ref31","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s10545-006-0508-4","article-title":"Pyridoxal 5\u2032-phosphate may be curative in early-onset epileptic encephalopathy","volume":"30","author":"Hoffmann","year":"2007","journal-title":"J. Inherit. Metab. Dis."},{"key":"2020120619075338700_ref32","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1007\/s10545-017-0061-3","article-title":"Vitamin B6 is essential for serine de novo biosynthesis","volume":"40","author":"Ramos","year":"2017","journal-title":"J. Inherit. Metab. Dis."},{"issue":"11","key":"2020120619075338700_ref33","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1161\/01.HYP.11.4.387","article-title":"Sympathetic stimulation and hypertension in the pyridoxine-deficient adult rat","author":"Paulose","year":"1988","journal-title":"Hypertension (Dallas, Tex. : 1979)"},{"key":"2020120619075338700_ref34","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.cbi.2011.02.016","article-title":"Aldehyde dehydrogenase 7A1 (ALDH7A1) attenuates reactive aldehyde and oxidative stress induced cytotoxicity","volume":"191","author":"Brocker","year":"2011","journal-title":"Chem. Biol. Interact."},{"key":"2020120619075338700_ref35","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S0003-2697(02)00537-7","article-title":"Simultaneous determination of methionine sulfoxide and methionine in blood plasma using gas chromatography-mass spectrometry","volume":"313","author":"Mashima","year":"2003","journal-title":"Anal. Biochem."},{"key":"2020120619075338700_ref36","doi-asserted-by":"crossref","DOI":"10.1038\/srep38299","article-title":"Methionine sulfoxides in serum proteins as potential clinical biomarkers of oxidative stress","volume":"6","author":"Suzuki","year":"2016","journal-title":"Sci. Rep."},{"key":"2020120619075338700_ref37","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1023\/A:1006947322342","article-title":"The glio-toxic mechanism of alpha-aminoadipic acid on cultured astrocytes","volume":"27","author":"Brown","year":"1998","journal-title":"J. Neurocytol."},{"key":"2020120619075338700_ref38","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1523\/JNEUROSCI.04-10-02650.1984","article-title":"The glutamate analogue alpha-aminoadipic acid is taken up by astrocytes before exerting its gliotoxic effect in vitro","volume":"4","author":"Huck","year":"1984","journal-title":"J. Neurosci."},{"key":"2020120619075338700_ref39","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/(SICI)1098-1136(199604)16:4<351::AID-GLIA7>3.0.CO;2-2","article-title":"Selective ablation of astrocytes by intracerebral injections of alpha-aminoadipate","volume":"16","author":"Khurgel","year":"1996","journal-title":"Glia"},{"key":"2020120619075338700_ref40","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1083\/jcb.201807204","article-title":"The lysine catabolite saccharopine impairs development by disrupting mitochondrial homeostasis","volume":"218","author":"Zhou","year":"2019","journal-title":"J. Cell Biol."},{"key":"2020120619075338700_ref41","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1684\/epd.2009.0280","article-title":"Electroencephalographic changes in pyridoxine-dependant epilepsy: new observations","volume":"11","author":"Naasan","year":"2009","journal-title":"Epileptic Disord."},{"key":"2020120619075338700_ref42","doi-asserted-by":"crossref","first-page":"F125","DOI":"10.1136\/fn.81.2.F125","article-title":"Pyridoxine dependent epilepsy: a suggestive electroclinical pattern","volume":"81","author":"Nabbout","year":"1999","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"2020120619075338700_ref43","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/ana.21568","article-title":"Folinic acid-responsive seizures are identical to pyridoxine-dependent epilepsy","volume":"65","author":"Gallagher","year":"2009","journal-title":"Ann. Neurol."},{"key":"2020120619075338700_ref44","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ejpn.2010.03.011","article-title":"Novel mutations in pyridoxine-dependent epilepsy","volume":"15","author":"Millet","year":"2011","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"2020120619075338700_ref45","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.ejpn.2011.05.011","article-title":"Long-term follow-up in two siblings with pyridoxine-dependent seizures associated with a novel ALDH7A1 mutation","volume":"15","author":"Yeghiazaryan","year":"2011","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"2020120619075338700_ref46","volume-title":"Nutrient Requirements of Laboratory Animals","author":"Mouse., N.R.C.U.S.o.L.A.N.N.R.o.t","year":"1995","edition":"4th revised edn"},{"key":"2020120619075338700_ref47","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s10545-016-9955-8","article-title":"The value of plasma vitamin B6 profiles in early onset epileptic encephalopathies","volume":"39","author":"Mathis","year":"2016","journal-title":"J. Inherit. Metab. Dis."},{"key":"2020120619075338700_ref48","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/epi.12083","article-title":"Clinical, biochemical, and molecular studies in pyridoxine-dependent epilepsy. 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