{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:56:16Z","timestamp":1792079776892,"version":"4.4.0"},"reference-count":107,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The X-chromosome-linked cell adhesion molecule L1 (L1CAM), a glycoprotein mainly expressed by neurons in the central and peripheral nervous systems, has been implicated in many neural processes, including neuronal migration and survival, neuritogenesis, synapse formation, synaptic plasticity and regeneration. L1 consists of extracellular, transmembrane and cytoplasmic domains. Proteolytic cleavage of L1\u2019s extracellular and transmembrane domains by different proteases generates several L1 fragments with different functions. We found that myelin basic protein (MBP) cleaves L1\u2019s extracellular domain, leading to enhanced neuritogenesis and neuronal survival in vitro. To investigate in vivo the importance of the MBP-generated 70 kDa fragment (L1-70), we generated mice with an arginine to alanine substitution at position 687 (L1\/687), thereby disrupting L1\u2019s MBP cleavage site and obliterating L1-70. Young adult L1\/687 males showed normal anxiety and circadian rhythm activities but enhanced locomotion, while females showed altered social interactions. Older L1\/687 males were impaired in motor coordination. Furthermore, L1\/687 male and female mice had a larger hippocampus, with more neurons in the dentate gyrus and more proliferating cells in the subgranular layer, while the thickness of the corpus callosum and the size of lateral ventricles were normal. In summary, subtle mutant morphological changes result in subtle behavioral changes.<\/jats:p>","DOI":"10.3390\/biom14040468","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T03:29:04Z","timestamp":1712806144000},"page":"468","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mice Mutated in the First Fibronectin Domain of Adhesion Molecule L1 Show Brain Malformations and Behavioral Abnormalities"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8150-4889","authenticated-orcid":false,"given":"Viviana","family":"Granato","sequence":"first","affiliation":[{"name":"Zentrum f\u00fcr Molekulare Neurobiologie, Universit\u00e4tsklinikum Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0657-1704","authenticated-orcid":false,"given":"Ludovica","family":"Congiu","sequence":"additional","affiliation":[{"name":"Zentrum f\u00fcr Molekulare Neurobiologie, Universit\u00e4tsklinikum Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Jakovcevski","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Anatomie und Klinische Morphologie, Universit\u00e4t Witten\/Herdecke, 58455 Witten, Germany"},{"name":"Department of Neuroanatomy and Molecular Brain Research, Institute of Anatomy, Ruhr-Universit\u00e4t Bochum, 44780 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Kleene","sequence":"additional","affiliation":[{"name":"Zentrum f\u00fcr Molekulare Neurobiologie, Universit\u00e4tsklinikum Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Schwindenhammer","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Anatomie und Klinische Morphologie, Universit\u00e4t Witten\/Herdecke, 58455 Witten, Germany"},{"name":"Department of Neuroanatomy and Molecular Brain Research, Institute of Anatomy, Ruhr-Universit\u00e4t Bochum, 44780 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8468-3854","authenticated-orcid":false,"given":"Luciana","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Zentrum f\u00fcr Molekulare Neurobiologie, Universit\u00e4tsklinikum Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Freitag","sequence":"additional","affiliation":[{"name":"Zentrum f\u00fcr Molekulare Neurobiologie, Universit\u00e4tsklinikum Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melitta","family":"Schachner","sequence":"additional","affiliation":[{"name":"Keck Center for Collaborative Neuroscience, Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08554, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Loers","sequence":"additional","affiliation":[{"name":"Zentrum f\u00fcr Molekulare Neurobiologie, Universit\u00e4tsklinikum Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nn1827","article-title":"Neural recognition molecules of the immunoglobulin superfamily: Signaling transducers of axon guidance and neuronal migration","volume":"10","author":"Maness","year":"2007","journal-title":"Nat. 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