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Over the last decade, sequencing studies including large cohorts of individuals with CHD have begun to unravel the genetic mechanisms underpinning CHD. This includes the identification of variants in <jats:italic>cyclin\u2010dependent kinase 13<\/jats:italic> (<jats:italic>CDK13<\/jats:italic>), in individuals with syndromic CHD. CDK13 encodes a serine\/threonine protein kinase. The cyclin partner of CDK13 is cyclin K; this complex is thought to be important in transcription and RNA processing. Pathogenic variants in <jats:italic>CDK13<\/jats:italic> cause CDK13\u2010related disorder in humans, characterised by intellectual disability and developmental delay, recognisable facial features, feeding difficulties and structural brain defects, with 35% of individuals having CHD. To obtain a greater understanding for the role that this essential protein kinase plays in embryonic heart development, we have analysed a presumed loss of function <jats:italic>Cdk13<\/jats:italic> transgenic mouse model (<jats:italic>Cdk13<\/jats:italic><jats:sup><jats:italic>tm1b<\/jats:italic><\/jats:sup>). The homozygous mutants were embryonically lethal in most cases by E15.5. X\u2010gal staining showed <jats:italic>Cdk13<\/jats:italic> expression localised to developing facial regions, heart and surrounding areas at E10.5, whereas at E12.5, it was more widely present. In the E15.5 heart, staining was seen throughout. RT\u2010qPCR showed significant reduction in <jats:italic>Cdk13<\/jats:italic> transcript expression in homozygous compared with WT and heterozygous hearts at E10.5 and E12.5. Detailed morphological 3D analysis of embryonic and postnatal hearts was performed using high\u2010resolution episcopic microscopy, which affords a more detailed analysis of structures such as cardiac valve leaflets and endocardial cushions, compared with more traditional histological techniques. We show that both the homozygous and heterozygous <jats:italic>Cdk13<\/jats:italic><jats:sup><jats:italic>tm1b<\/jats:italic><\/jats:sup> mutants exhibit a range of CHD, including ventricular septal defects, bicuspid aortic valve, double outlet right ventricle and atrioventricular septal defects. 100% (<jats:italic>n<\/jats:italic>\u2009=\u20094) of homozygous hearts displayed CHD. Differential expression was seen in <jats:italic>Cdk13<\/jats:italic><jats:sup><jats:italic>tm1b<\/jats:italic><\/jats:sup> homozygous mutants for two genes known to be necessary for normal heart development. The types of defects, and the presence of CHD in heterozygous mice (17.02%, <jats:italic>n<\/jats:italic>\u2009=\u20098\/47), are consistent with the CDK13\u2010related disorder phenotype in humans. This study provides important insights into the effects of reduced function of <jats:italic>CDK13<\/jats:italic> in the mouse heart and contributes to our understanding of the mechanism behind this disorder as a cause of CHD.<\/jats:p>","DOI":"10.1111\/joa.14175","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T15:04:23Z","timestamp":1731942263000},"page":"616-630","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cyclin\u2010dependent kinase 13 is indispensable for normal mouse heart development"],"prefix":"10.1111","volume":"246","author":[{"given":"Qazi","family":"Waheed\u2010Ullah","sequence":"first","affiliation":[{"name":"School of Life Sciences, Faculty of Medicine and Health Sciences University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Wilsdon","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Faculty of Medicine and Health Sciences University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aseel","family":"Abbad","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Faculty of Medicine and Health Sciences University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Rochette","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Faculty of Medicine and Health Sciences University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Bu'Lock","sequence":"additional","affiliation":[{"name":"East Midlands Congenital Heart Centre University Hospitals of Leicester NHS Trust  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma Ali","family":"Saed","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Faculty of Medicine and Health Sciences University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc\u2010Phillip","family":"Hitz","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics Carl von Ossietzky University Oldenburg  Oldenburg Germany"},{"name":"Department of Congenital Heart Disease and Paediatric Cardiology University Hospital of Schleswig\u2010Holstein  Kiel Germany"},{"name":"German Centre for Cardiovascular Research (DZHK)  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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