{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:00:45Z","timestamp":1790593245623,"version":"4.1.0"},"reference-count":159,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Phenylketonuria (PKU) is a rare metabolic disorder resulting from a mutation in the gene encoding the enzyme phenylalanine hydroxylase (PAH), resulting in very high phenylalanine (Phe) levels in blood and brain. A PKU mutant mouse model was developed via N\u2010ethyl\u2010N\u2010nitrosourea (ENU) mutagenesis, mimicking the high brain Phe content seen in classic PKU patients. A large variety of behavioral tasks have been employed to explore the behavioral phenotype of the Pah\n                    <jats:sup>enu2<\/jats:sup>\n                    mouse. The purpose of this scoping review is to provide an overview of the behavioral performance of PKU mutant mice. We addressed three aims: (1) provide an overview of the behavioral tasks that have been performed with these mice, (2) summarize the reported findings across behavioral domains, (3) identify gaps and future perspectives for behavioral testing in the field of preclinical PKU. Peer\u2010reviewed studies published in English up to May 2026 were identified through structured searches in PubMed and Web of Science, supplemented by free\u2010text searches. Studies were eligible if they used adult untreated Pah\n                    <jats:sup>enu2<\/jats:sup>\n                    mice and included a comparison with wild\u2010type controls. Twenty\u2010two studies were included. Nest\u2010building behavior and balance beam performance always reveal deficits in PKU mutant mice, whereas most studies found no significant anxiety\u2010like phenotypes. A striking variation in cognitive test performance was found across studies, despite high Phe levels. In conclusion, balance beam and nest\u2010building tests reliably demonstrate deficits in Pah\n                    <jats:sup>enu2<\/jats:sup>\n                    mice, while other cognitive findings remain variable. The Pah\n                    <jats:sup>enu2<\/jats:sup>\n                    model retains value for future behavioral research and benchmarking of novel PKU models.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70229","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T04:38:03Z","timestamp":1785991083000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Behavioral Phenotyping of the Pah\n                    <sup>enu2<\/sup>\n                    Mouse Model for Phenylketonuria\u2014A Scoping Review and Future Perspectives"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3271-9497","authenticated-orcid":false,"given":"Junfei","family":"Cao","sequence":"first","affiliation":[{"name":"Neurobiology Expertise Group, Groningen Institute for Evolutionary Life Sciences (GELIFES) University of Groningen  Groningen the 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