Recognition deficits in mice carrying mutations of genes encoding BLOC-1 subunits pallidin or dysbindin.
S SpiegelA ChiuA S JamesJ D JentschKatherine H KarlsgodtPublished in: Genes, brain, and behavior (2015)
Numerous studies have implicated DTNBP1, the gene encoding dystrobrevin-binding protein or dysbindin, as a candidate risk gene for schizophrenia, though this relationship remains somewhat controversial. Variation in dysbindin, and its location on chromosome 6p, has been associated with cognitive processes, including those relying on a complex system of glutamatergic and dopaminergic interactions. Dysbindin is one of the seven protein subunits that comprise the biogenesis of lysosome-related organelles complex 1 (BLOC-1). Dysbindin protein levels are lower in mice with null mutations in pallidin, another gene in the BLOC-1, and pallidin levels are lower in mice with null mutations in the dysbindin gene, suggesting that multiple subunit proteins must be present to form a functional oligomeric complex. Furthermore, pallidin and dysbindin have similar distribution patterns in a mouse and human brain. Here, we investigated whether the apparent correspondence of pallid and dysbindin at the level of gene expression is also found at the level of behavior. Hypothesizing a mutation leading to underexpression of either of these proteins should show similar phenotypic effects, we studied recognition memory in both strains using the novel object recognition task (NORT) and social novelty recognition task (SNRT). We found that mice with a null mutation in either gene are impaired on SNRT and NORT when compared with wild-type controls. These results support the conclusion that deficits consistent with recognition memory impairment, a cognitive function that is impaired in schizophrenia, result from either pallidin or dysbindin mutations, possibly through degradation of BLOC-1 expression and/or function.
Keyphrases
- wild type
- genome wide
- copy number
- binding protein
- genome wide identification
- gene expression
- high fat diet induced
- bipolar disorder
- healthcare
- working memory
- escherichia coli
- poor prognosis
- genome wide analysis
- magnetic resonance
- insulin resistance
- mental health
- protein protein
- small molecule
- long non coding rna
- mass spectrometry
- diffusion weighted imaging