{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:25:55Z","timestamp":1790357155461,"version":"4.1.0"},"reference-count":33,"publisher":"CSIRO Publishing","issue":"10","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":1813,"URL":"https:\/\/doi.org\/10.1071\/journalslicense"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,26]]},"abstract":"<jats:p>The PDZ-binding kinase (PBK) protein is localised exclusively in spermatogenic cells, such as spermatogonia, spermatocytes and round spermatids, of the adult testis. However, its role in male fertility remains unknown. Analysis of adult Pbk-knockout (KO) male mice showed no significant difference in the weight of the testes, epididymis and seminal vesicle compared with adult wild-type (WT) mice. There were no significant differences in testis morphology, tubule diameter and the number of offspring born to females mated with KO or WT male mice. Sperm number, motility and morphology did not differ significantly between KO and WT mice. The oocyte fertilisation rate and embryo development following IVF were comparable between groups fertilised using spermatozoa from KO versus WT mice (P &amp;gt; 0.05). Further analysis revealed that the phosphorylation of the mitogen-activated protein kinases (MAPKs) p38 kinase, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinases was dysregulated in the testis of KO mice. In conclusion, Pbk-KO male mice are fertile and their spermatozoa and testis do not show any morphological and functional abnormalities despite the dysregulated phosphorylation of MAPKs. It is likely that functional redundancy of PBK and overlapping substrate specificities of the MAPK superfamily compensated for the loss of PBK from the testis.<\/jats:p>","DOI":"10.1071\/rd19445","type":"journal-article","created":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T17:56:28Z","timestamp":1591638988000},"page":"893-902","source":"Crossref","is-referenced-by-count":6,"title":["Deletion of the PDZ-binding kinase (Pbk) gene does not affect male fertility in mice"],"prefix":"10.1071","volume":"32","author":[{"given":"Yuka","family":"Miki","sequence":"first","affiliation":[{"name":"ALaboratory of Reproductive Biology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalitha","family":"Devi","sequence":"additional","affiliation":[{"name":"BMouse Genomics Resource Laboratory, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka-ken 411-8540, Japan."},{"name":"CLaboratory for the Conservation of Endangered Species, Centre for Cellular and Molecular Biology, Council for Scientific and Industrial Research, Uppal Road, Hyderabad 500 007, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Imai","sequence":"additional","affiliation":[{"name":"BMouse Genomics Resource Laboratory, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka-ken 411-8540, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naojiro","family":"Minami","sequence":"additional","affiliation":[{"name":"ALaboratory of Reproductive Biology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Koide","sequence":"additional","affiliation":[{"name":"BMouse Genomics Resource Laboratory, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka-ken 411-8540, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7485-5392","authenticated-orcid":true,"given":"Sandeep","family":"Goel","sequence":"additional","affiliation":[{"name":"ALaboratory of Reproductive Biology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan."},{"name":"CLaboratory for the Conservation of Endangered Species, Centre for Cellular and Molecular Biology, Council for Scientific and Industrial Research, Uppal Road, Hyderabad 500 007, India."},{"name":"DCorresponding author. Email: sandeep@ccmb.res.in"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"67","published-online":{"date-parts":[[2020,6,9]]},"reference":[{"key":"2025102820112361100_R1","doi-asserted-by":"publisher","first-page":"21525","DOI":"10.1074\/JBC.M909629199","article-title":"Cloning and expression of a novel MAPKK-like protein kinase, lymphokine-activated killer T-cell-originated protein kinase, specifically expressed in the testis and activated lymphoid cells.","volume":"275","author":"Abe","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2025102820112361100_R2","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/J.MCE.2007.11.011","article-title":"Mitogen activated protein kinases (MAPKs) as regulators of spermatogenesis and spermatozoa functions.","volume":"282","author":"Almog","year":"2008","journal-title":"Mol. Cell. Endocrinol."},{"key":"2025102820112361100_R3","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1023\/A:1026432211012","article-title":"Localization of penultimate carbohydrate residues in zona pellucida and acrosomes by means of lectin cytochemistry and enzymatic treatments.","volume":"29","author":"Avil\u00e9s","year":"1997","journal-title":"Histochem. J."},{"key":"2025102820112361100_R4","doi-asserted-by":"publisher","first-page":"15594","DOI":"10.18632\/ONCOTARGET.3709","article-title":"PBK\/TOPK enhances aggressive phenotype in prostate cancer via beta-catenin-TCF\/LEF-mediated matrix metalloproteinases production and invasion.","volume":"6","author":"Brown-Clay","year":"2015","journal-title":"Oncotarget"},{"key":"2025102820112361100_R5","doi-asserted-by":"publisher","first-page":"2605","DOI":"10.1038\/S41598-017-02604-4","article-title":"Dysregulation of angiogenesis-specific signalling in adult testis results in xenograft degeneration.","volume":"7","author":"Devi","year":"2017","journal-title":"Sci. Rep."},{"key":"2025102820112361100_R6","doi-asserted-by":"publisher","first-page":"10773","DOI":"10.1523\/JNEUROSCI.3207-05.2005","article-title":"PBK\/TOPK, a proliferating neural progenitor-specific mitogen-activated protein kinase kinase.","volume":"25","author":"Dougherty","year":"2005","journal-title":"J. Neurosci."},{"key":"2025102820112361100_R7","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1095\/BIOLREPROD.110.086801","article-title":"A male-specific role for p38 mitogen-activated protein kinase in germ cell sex differentiation in mice.","volume":"83","author":"Ewen","year":"2010","journal-title":"Biol. Reprod."},{"key":"2025102820112361100_R8","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1111\/J.1440-169X.2005.00834.X","article-title":"Expression and phosphorylation of TOPK during spermatogenesis.","volume":"47","author":"Fujibuchi","year":"2005","journal-title":"Dev. Growth Differ."},{"key":"2025102820112361100_R9","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/S13059-016-1012-2","article-title":"Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR.","volume":"17","author":"Haeussler","year":"2016","journal-title":"Genome Biol."},{"key":"2025102820112361100_R10","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1002\/MRD.1080410214","article-title":"Preimplantation development of mouse embryos in KSOM: augmentation by amino acids and analysis of gene expression.","volume":"41","author":"Ho","year":"1995","journal-title":"Mol. Reprod. Dev."},{"key":"2025102820112361100_R11","first-page":"351","article-title":"Effects of androgen and estradiol administration on the weight of the ventral prostate, seminal vesicles, and testes of immature rats.","volume":"14","author":"Jackson","year":"1977","journal-title":"Invest. Urol."},{"key":"2025102820112361100_R12","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1095\/BIOLREPROD.108.068833","article-title":"Role of caspase 2 in apoptotic signaling in primate and murine germ cells.","volume":"79","author":"Johnson","year":"2008","journal-title":"Biol. Reprod."},{"key":"2025102820112361100_R13","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/J.MOLMED.2009.02.002","article-title":"Mitogen-activated protein kinases in male reproductive function.","volume":"15","author":"Li","year":"2009","journal-title":"Trends Mol. Med."},{"key":"2025102820112361100_R14","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/J.MOLMED.2009.02.002","article-title":"Mitogen-activated protein kinases in male reproductive function.","volume":"15","author":"Li","year":"2009","journal-title":"Trends Mol. Med."},{"key":"2025102820112361100_R15","doi-asserted-by":"publisher","first-page":"29601","DOI":"10.1074\/JBC.M111.225813","article-title":"T-LAK cell-originated protein kinase (TOPK) phosphorylation of MKP1 protein prevents solar ultraviolet light-induced inflammation through inhibition of the p38 protein signaling pathway.","volume":"286","author":"Li","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2025102820112361100_R16","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1093\/BIOINFORMATICS\/BTU743","article-title":"CRISPRdirect: software for designing CRISPR\/Cas guide RNA with reduced off-target sites.","volume":"31","author":"Naito","year":"2015","journal-title":"Bioinformatics"},{"key":"2025102820112361100_R17","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/J.BCMD.2003.10.004","article-title":"Protein expression of PDZ-binding kinase is up-regulated in hematologic malignancies and strongly down-regulated during terminal differentiation of HL-60 leukemic cells.","volume":"32","author":"Nandi","year":"2004","journal-title":"Blood Cells Mol. Dis."},{"key":"2025102820112361100_R18","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/S41419-019-1782-Z","article-title":"Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis.","volume":"10","author":"Ni","year":"2019","journal-title":"Cell Death Dis."},{"key":"2025102820112361100_R19","doi-asserted-by":"publisher","first-page":"6457","DOI":"10.21873\/ANTICANRES.11244","article-title":"Overexpression of PBK\/TOPK contributes to tumor development and poor outcome of esophageal squamous cell carcinoma.","volume":"36","author":"Ohashi","year":"2016","journal-title":"Anticancer Res."},{"key":"2025102820112361100_R20","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/BJC.2016.394","article-title":"Overexpression of PBK\/TOPK relates to tumour malignant potential and poor outcome of gastric carcinoma.","volume":"116","author":"Ohashi","year":"2017","journal-title":"Br. J. Cancer"},{"key":"2025102820112361100_R21","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1038\/NPROT.2013.143","article-title":"Genome engineering using the CRISPR-Cas9 system.","volume":"8","author":"Ran","year":"2013","journal-title":"Nat. Protoc."},{"key":"2025102820112361100_R22","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/J.MCE.2006.12.041","article-title":"The expression of the testis-specific Dyrk4 kinase is highly restricted to step 8 spermatids but is not required for male fertility in mice.","volume":"267","author":"Sacher","year":"2007","journal-title":"Mol. Cell. Endocrinol."},{"key":"2025102820112361100_R23","article-title":"The cancer\/testis genes: review, standardization, and commentary.","volume":"4","author":"Scanlan","year":"2004","journal-title":"Cancer Immun."},{"key":"2025102820112361100_R24","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1242\/JCS.059949","article-title":"Functional transformation of the chromatoid body in mouse spermatids requires testis-specific serine\/threonine kinases.","volume":"123","author":"Shang","year":"2010","journal-title":"J. Cell Sci."},{"key":"2025102820112361100_R25","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1006\/BCMD.2001.0452","article-title":"PBK\/TOPK is a novel mitotic kinase which is upregulated in Burkitt\u2019s lymphoma and other highly proliferative malignant cells.","volume":"27","author":"Simons-Evelyn","year":"2001","journal-title":"Blood Cells Mol. Dis."},{"key":"2025102820112361100_R26","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/NRC1669","article-title":"Cancer\/testis antigens, gametogenesis and cancer.","volume":"5","author":"Simpson","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"2025102820112361100_R27","doi-asserted-by":"publisher","first-page":"2741","DOI":"10.1242\/JCS.047225","article-title":"Tssk6 is required for Izumo relocalization and gamete fusion in the mouse.","volume":"122","author":"Sosnik","year":"2009","journal-title":"J. Cell Sci."},{"key":"2025102820112361100_R28","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/S0952-7915(96)80131-2","article-title":"Mitogen-activated protein kinase cascades and regulation of gene expression.","volume":"8","author":"Su","year":"1996","journal-title":"Curr. Opin. Immunol."},{"key":"2025102820112361100_R29","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1242\/DEV.120493","article-title":"CHD1 acts via the Hmgpi pathway to regulate mouse early embryogenesis.","volume":"142","author":"Suzuki","year":"2015","journal-title":"Development"},{"key":"2025102820112361100_R30","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1093\/MOLEHR\/GAU097","article-title":"Tssk4 is essential for maintaining the structural integrity of sperm flagellum.","volume":"21","author":"Wang","year":"2015","journal-title":"Mol. Hum. Reprod."},{"key":"2025102820112361100_R31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/J.YDBIO.2005.08.001","article-title":"Mitogen-activated protein kinases, adherens junction dynamics, and spermatogenesis: a review of recent data.","volume":"286","author":"Wong","year":"2005","journal-title":"Dev. Biol."},{"key":"2025102820112361100_R32","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/J.YDBIO.2008.03.043","article-title":"TSKS concentrates in spermatid centrioles during flagellogenesis.","volume":"319","author":"Xu","year":"2008","journal-title":"Dev. Biol."},{"key":"2025102820112361100_R33","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/S1357-2725(01)00005-X","article-title":"PDZ-binding kinase participates in spermatogenesis.","volume":"33","author":"Zhao","year":"2001","journal-title":"Int. J. Biochem. Cell Biol."}],"container-title":["Reproduction, Fertility and Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/connectsci.au\/rd\/article-pdf\/32\/10\/893\/316487\/rd19445.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/connectsci.au\/rd\/article-pdf\/32\/10\/893\/316487\/rd19445.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:11:46Z","timestamp":1761696706000},"score":1,"resource":{"primary":{"URL":"https:\/\/connectsci.au\/rd\/article\/32\/10\/893\/50641\/Deletion-of-the-PDZ-binding-kinase-Pbk-gene-does"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,9]]},"references-count":33,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,6,26]]}},"URL":"https:\/\/doi.org\/10.1071\/rd19445","relation":{},"ISSN":["1031-3613","1448-5990"],"issn-type":[{"value":"1031-3613","type":"print"},{"value":"1448-5990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,9]]}}}