Knockout or Knock-in? A Truncated D2 Receptor Protein Is Expressed in the Brain of Functional D2 Receptor Knockout Mice

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dc.contributor.authorSanchez, Natalia
dc.contributor.authorOlivares-Costa, Montserrat
dc.contributor.authorGonzalez, Marcela P.
dc.contributor.authorMunita, Roberto
dc.contributor.authorEscobar, Angelica P.
dc.contributor.authorMeza, Rodrigo
dc.contributor.authorHerrera-Rojas, Mauricio
dc.contributor.authorAlbornoz, Jessica
dc.contributor.authorMerello, Gianluca
dc.contributor.authorAndres, Maria E.
dc.date.accessioned2025-01-20T22:22:04Z
dc.date.available2025-01-20T22:22:04Z
dc.date.issued2021
dc.description.abstractNull mice for the dopamine D2 receptor (D2R) have been instrumental in understanding the function of this protein. For our research, we obtained the functional D2R knockout mouse strain described initially in 1997. Surprisingly, our biochemical characterization showed that this mouse strain is not a true knockout. We determined by sequence analysis of the rapid 3 ' amplification of cDNA ends that functional D2R knockout mice express transcripts that lack only the eighth exon. Furthermore, immunofluorescence assays showed a D2R-like protein in the brain of functional D2R knockout mice. We verified by immunofluorescence that the recombinant truncated D2R is expressed in HEK293T cells, showing intracellular localization, colocalizing in the Golgi apparatus and the endoplasmic reticulum, but with less presence in the Golgi apparatus compared to the native D2R. As previously reported, functional D2R knockout mice are hypoactive and insensitive to the D2R agonist quinpirole. Concordantly, microdialysis studies confirmed that functional D2R knockout mice have lower extracellular dopamine levels in the striatum than the native mice. In conclusion, functional D2R knockout mice express transcripts that lead to a truncated D2R protein lacking from the sixth transmembrane domain to the C-terminus. We share these findings to avoid future confusion and the community considers this mouse strain in D2R traffic and protein-protein interaction studies.
dc.fuente.origenWOS
dc.identifier.doi10.3390/neurosci2020014
dc.identifier.eissn2673-4087
dc.identifier.urihttps://doi.org/10.3390/neurosci2020014
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94667
dc.identifier.wosidWOS:001109286800001
dc.issue.numero2
dc.language.isoen
dc.pagina.final206
dc.pagina.inicio193
dc.revistaNeurosci
dc.rightsacceso restringido
dc.subjectdopamine 2 receptor
dc.subjectfunctional knockout
dc.subjecttruncated protein
dc.titleKnockout or Knock-in? A Truncated D2 Receptor Protein Is Expressed in the Brain of Functional D2 Receptor Knockout Mice
dc.typeartículo
dc.volumen2
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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