Poor mother-offspring relationships in rats with <i>Cacna1a</i> mutation

Abstract

Homozygous Groggy dams, which carry a Cacna1a missense mutation, often show no interest in their offspring, leading to frequent offspring deaths due to lack of nurturing. The present study aimed to clarify whether the Cacna1a mutation contributes to impaired attachment behaviors between dam and offspring. The open field test showed that homozygous female rats exhibited markedly short travel distance, whereas no difference was found between the motor activity of heterozygous females and that of wild types (WT). A series of behavioral tests was performed to compare the mother-offspring relationship between WT and heterozygous rats. Performance in the pup retrieval test was significantly less successful in heterozygous than WT dams. During the experiment, heterozygous dams spent significantly less time licking and crouching than WT dams. The offspring dam-seeking behavior test revealed that heterozygous pups' vocalizations were significantly less frequent and shorter than those of WT pups. Although no significant difference was found between WT and heterozygous offspring in the olfactory sense test, using a piece of chocolate, heterozygous pups took significantly longer to reach a sample of the dam's bedding. Taken together, these findings suggest that the Cacna1a mutation impairs both the dam's maternal behavior and the offspring's attachment behavior toward the dam.

The genotype–phenotype correlations of the CACNA1A-related neurodevelopmental disorders: a small case series and literature reviews

“…CACNA1A single nucleotide polymorphisms are among the top causes of ASD in all VGCCs ( Liao and Li, 2020 ). Homozygous Groggy dams carrying Cacna1a missense mutation have no concern for their babies leading to their deaths, which somehow present like ASD ( Kawakami et al, 2020 ). Auts2 knockout mice have small and malformed cerebella with reduced expression of Cacna1a protein, and impaired motor learning and communication ( Yamashiro et al, 2020 ).…”