title: Mice with Dab1 or Vldlr insufficiency exhibit abnormal neonatal vocalization patterns.
abstract: Genetic and epigenetic changes in components of the Reelin-signaling pathway (RELN, DAB1) are associated with autism spectrum disorder (ASD) risk. Social communication deficits are a key component of the ASD diagnostic criteria, but the underlying neurogenetic mechanisms remain unknown. Reln insufficient mice exhibit ASD-like behavioral phenotypes including altered neonatal vocalization patterns. Reelin affects multiple pathways including through the receptors, Very low-density lipoprotein receptor (Vldlr), Apolipoprotein receptor 2 (Apoer2), and intracellular signaling molecule Disabled-1 (Dab1). As Vldlr was previously implicated in avian vocalization, here we investigate vocalizations of neonatal mice with a reduction or absence of these components of the Reelin-signaling pathway. Mice with low or no Dab1 expression exhibited reduced calling rates, altered call-type usage, and differential vocal development trajectories. Mice lacking Vldlr expression also had altered call repertoires, and this effect was exacerbated by deficiency in Apoer2. Together with previous findings, these observations 1) solidify a role for Reelin in vocal communication of multiple species, 2) point to the canonical Reelin-signaling pathway as critical for development of normal neonatal calling patterns in mice, and 3) suggest that mutants in this pathway could be used as murine models for Reelin-associated vocal deficits in humans.
authors.affiliation: Molecular, Cellular and Integrative Physiology Graduate Program, University of California, Los Angeles, USA.|Department of Integrative Biology and Physiology, University of California, Los Angeles, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Fraley
authors.affiliation: Molecular, Cellular and Integrative Physiology Graduate Program, University of California, Los Angeles, USA.|Department of Integrative Biology and Physiology, University of California, Los Angeles, USA.
authors.forename: Z D
authors.initials: ZD
authors.lastname: Burkett
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, USA.
authors.forename: N F
authors.initials: NF
authors.lastname: Day
authors.affiliation: Undergraduate Interdepartmental Program in Neuroscience, University of California, Los Angeles, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Schwartz
authors.affiliation: Molecular, Cellular and Integrative Physiology Graduate Program, University of California, Los Angeles, USA.|Department of Integrative Biology and Physiology, University of California, Los Angeles, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Phelps
authors.affiliation: Molecular, Cellular and Integrative Physiology Graduate Program, University of California, Los Angeles, USA.|Department of Integrative Biology and Physiology, University of California, Los Angeles, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: White
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D018628:Gene Dosage; D005838:Genotype; D026502:LDL-Receptor Related Proteins / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism; D014828:Vocalization, Animal
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D026502:LDL-Receptor Related Proteins; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; D000091042:Reelin Protein; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases