Mice with Dab1 or Vldlr insufficiency exhibit abnormal neonatal vocalization patterns.

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Genetic and epigenetic alterations in the Reelin-signaling pathway (RELN, DAB1) are linked to autism spectrum disorder (ASD) risk.
• Social communication deficits are a core feature of ASD, but their neurogenetic underpinnings are not fully understood.
• Reelin signaling influences multiple pathways, including those involving Very low-density lipoprotein receptor (Vldlr) and Apolipoprotein receptor 2 (Apoer2).

Purpose of the Study:

• To investigate the role of the Reelin-signaling pathway in neonatal vocalizations.
• To examine vocalization patterns in mice with reduced or absent expression of DAB1, VLDLR, and APOER2.
• To explore the Reelin pathway's contribution to vocal communication deficits relevant to ASD.

Main Methods:

• Analysis of neonatal mouse vocalizations.
• Comparison of calling rates, call-type usage, and developmental trajectories in wild-type and mutant mice.
• Assessment of mice with deficiencies in Disabled-1 (Dab1), Very low-density lipoprotein receptor (Vldlr), and Apolipoprotein receptor 2 (Apoer2).

Main Results:

• Mice with low or no Dab1 expression exhibited reduced calling rates and altered call-type usage.
• Vocalization development trajectories differed significantly in Dab1-deficient mice.
• Mice lacking Vldlr expression showed altered call repertoires, an effect worsened by Apoer2 deficiency.

Conclusions:

• The Reelin-signaling pathway is crucial for the development of normal neonatal vocal patterns in mice.
• These findings solidify Reelin's role in vocal communication across species.
• Mutants in the Reelin pathway may serve as valuable models for studying Reelin-associated vocal deficits in humans with ASD.