title: Characterisation of Cdkl5 transcript isoforms in rat.
abstract: CDKL5 deficiency is a severe neurological disorder caused by mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5). The predominant human CDKL5 brain isoform is a 9.7kb transcript comprised of 18 exons with a large 6.6kb 3'-untranslated region (UTR). Mammalian models of CDKL5 disorder are currently limited to mouse, and little is known about Cdkl5 in other organisms used to model neurodevelopmental disorders, such as rat. In this study we characterise, both bioinformatically and experimentally, the rat Cdkl5 gene structure and its associated transcript isoforms. New exonic regions, splice sites and UTRs are described, confirming the presence of four distinct transcript isoforms. The predominant isoform in the brain, which we name rCdkl5_1, is orthologous to the human hCDKL5_1 and mouse mCdkl5_1 isoforms and is the most highly expressed isoform across all brain regions tested. This updated gene model of Cdkl5 in rat provides a framework for studies into its protein products and provides a reference for the development of molecular therapies for testing in rat models of CDKL5 disorder.
authors.affiliation: Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. Electronic address: ralph.hector@glasgow.ac.uk.
authors.forename: Ralph D
authors.initials: RD
authors.lastname: Hector
authors.affiliation: Patrick Wild Centre, University of Edinburgh, Edinburgh, UK; Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK; Centre for Brain Development and Repair, The Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India. Electronic address: owen.dando@ed.ac.uk.
authors.forename: Owen
authors.initials: O
authors.lastname: Dando
authors.affiliation: Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. Electronic address: tuula.ritakari@gmail.com.
authors.forename: Tuula E
authors.initials: TE
authors.lastname: Ritakari
authors.affiliation: Patrick Wild Centre, University of Edinburgh, Edinburgh, UK; Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK; Centre for Brain Development and Repair, The Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India. Electronic address: pkind@exseed.ed.ac.uk.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Kind
authors.affiliation: School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK. Electronic address: Mark.Bailey@glasgow.ac.uk.
authors.forename: Mark E S
authors.initials: ME
authors.lastname: Bailey
authors.affiliation: Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. Electronic address: stuart.cobb@glasgow.ac.uk.
authors.forename: Stuart R
authors.initials: SR
authors.lastname: Cobb
mesh_terms: D020413:3' Untranslated Regions; D017398:Alternative Splicing; D000818:Animals; D001923:Brain Chemistry; D005091:Exons; D015870:Gene Expression; D006801:Humans; D007438:Introns; D051379:Mice; D016366:Open Reading Frames; D009928:Organ Specificity; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D022821:RNA Splice Sites; D051381:Rats; D012689:Sequence Homology, Nucleic Acid
chemical_list: D020413:3' Untranslated Regions; D020033:Protein Isoforms; D022821:RNA Splice Sites; D017346:Protein Serine-Threonine Kinases; C551435:CDKL5 protein, rat
keywords: CDKL5; CDKL5 disorder; Expression; Neurodevelopmental; Neurological