{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:42:24Z","timestamp":1790959344566,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T00:00:00Z","timestamp":1627862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Homeodomain-interacting protein kinase 2 (HIPK2) is a serine-threonine kinase that phosphorylates various transcriptional and chromatin regulators, thus modulating numerous important cellular processes, such as proliferation, apoptosis, DNA damage response, and oxidative stress. The role of HIPK2 in the pathogenesis of cancer and fibrosis is well established, and evidence of its involvement in the homeostasis of multiple organs has been recently emerging. We have previously demonstrated that Hipk2-null (Hipk2-KO) mice present cerebellar alterations associated with psychomotor abnormalities and that the double ablation of HIPK2 and its interactor HMGA1 causes perinatal death due to respiratory failure. To identify other alterations caused by the loss of HIPK2, we performed a systematic morphological analysis of Hipk2-KO mice. Post-mortem examinations and histological analysis revealed that Hipk2 ablation causes neuronal loss, neuronal morphological alterations, and satellitosis throughout the whole central nervous system (CNS); a myopathic phenotype characterized by variable fiber size, mitochondrial proliferation, sarcoplasmic inclusions, morphological alterations at neuromuscular junctions; and a cardiac phenotype characterized by fibrosis and cardiomyocyte hypertrophy. These data demonstrate the importance of HIPK2 in the physiology of skeletal and cardiac muscles and of different parts of the CNS, thus suggesting its potential relevance for different new aspects of human pathology.<\/jats:p>","DOI":"10.3390\/ijms22158294","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T08:44:11Z","timestamp":1627893851000},"page":"8294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Phenotypic Effects of Homeodomain-Interacting Protein Kinase 2 Deletion in Mice"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8118-9807","authenticated-orcid":false,"given":"Davide","family":"De Biase","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Valente","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Conte","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Cammarota","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Boccella","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"D\u2019Esposito","sequence":"additional","affiliation":[{"name":"Centro Servizi Veterinari, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"d\u2019Aquino","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orlando","family":"Paciello","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5332-6774","authenticated-orcid":false,"given":"Simona","family":"Paladino","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna Maria","family":"Pierantoni","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25875","DOI":"10.1074\/jbc.273.40.25875","article-title":"Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors","volume":"273","author":"Kim","year":"1998","journal-title":"J. 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