Gene models of schizophrenia: DISC1 mouse models

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Disrupted in Schizophrenia-1 (DISC1) is a major susceptibility gene for schizophrenia (SZ).
• DISC1 functions as a hub protein crucial for nervous system development.
• NRG1 and ErbB4 are also implicated as SZ susceptibility genes with similar neurodevelopmental roles.

Purpose of the Study:

• To review existing DISC1 mouse models and their relevance to schizophrenia.
• To compare DISC1 models with NRG1 and ErbB4 mouse models.
• To outline future research directions for understanding DISC1's role in SZ.

Main Methods:

• Analysis of seven existing DISC1 mouse models.
• Comparison of neuroanatomical and behavioral abnormalities across DISC1, NRG1, and ErbB4 mouse models.
• Review of current literature on DISC1, NRG1, and ErbB4 in neurodevelopment.

Main Results:

• All seven DISC1 mouse models exhibit neuroanatomical and behavioral abnormalities relevant to SZ.
• NRG1 and ErbB4 mouse models show similar neurodevelopmental and behavioral deficits.
• Most DISC1 models require further comprehensive characterization.

Conclusions:

• DISC1, NRG1, and ErbB4 mouse models offer valuable insights into schizophrenia pathogenesis.
• Future research should focus on further characterizing existing models, utilizing inducible systems, generating a DISC1 knockout, and combining models with other risk factors.