Abnormal behaviours relevant to neurodevelopmental disorders in Kirrel3-knockout mice

Area of Science:

• Neuroscience
• Genetics
• Behavioral Science

Background:

• The KIRREL3 gene plays a role in nervous system development, including neuronal migration and synapse formation.
• Mutations in KIRREL3 are linked to neurodevelopmental disorders like autism spectrum disorder (ASD) and intellectual disability.

Purpose of the Study:

• To investigate the causal relationship between KIRREL3 deficiency and behavioral abnormalities relevant to neurodevelopmental disorders.
• To characterize the detailed behavioral phenotypes of global Kirrel3-knockout mice (Kirrel3-/-).

Main Methods:

• Generation of global Kirrel3-knockout (Kirrel3-/-) mice.
• Comprehensive behavioral analysis including social approach, ultrasonic communication, locomotor activity, rotarod, acoustic startle, and anxiety/memory tests.

Main Results:

• Kirrel3-/- mice showed social approach preference for mice over objects but lacked preference for stranger over familiar mice.
• Significant impairments in ultrasonic vocalizations (pup-to-mother, courtship, intruder response) were observed.
• Kirrel3-/- mice exhibited increased locomotor activity, repetitive rearing, hypersensitivity to acoustic stimuli, and enhanced rotarod performance.
• Anxiety-related behaviors and spatial/fear memory were unaffected.

Conclusions:

• Kirrel3 deficiency in mice leads to autistic-like behaviors, encompassing social and communication deficits, repetitive actions, sensory processing abnormalities, and hyperactivity.
• These findings highlight Kirrel3's crucial role in neurodevelopment and provide a valuable mouse model for studying related human disorders.