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Heterozygous Deletion of α -Neurexin I
or α -Neurexin II Results in Behaviors
Relevant to Autism and Schizophrenia
Presented by
Muhammad Younis
Background
• Schizophrenia is a mental disorder characterized by
abnormal social behavior and failure to understand
reality.
• Autism is a neurodevelopmental disorder
characterized by impaired social interaction.
• Human genetic studies have found heterozygous
deletions affecting NRXN1 and NRXN2, encoding -
neurexin I (Nrxn1) and -neurexin II (Nrxn2), in
individuals with autism spectrum disorders and
schizophrenia.
α -Neurexin HET Mice Have Altered Social
Behaviors
HET= Heterozygous deletion of Nrxn1α or Nrxn2α
α -Neurexin HET Mice Show Limited
Impairments in Cognition
Passive avoidance testDiscrimination memory
α -Neurexin HET Mice Have Unaltered
Ambulation and Anxiety
Nrxn HET mice do not display anxiety like
behaviors
Plus maze
α -Neurexin HET Mice Show Intact
Prepulse Inhibition
• Prepulse inhibition of startle are operational measures of sensory gating.
• Sensory gating is disrupted in schizophrenia,
• Acoustic startle reactivity was measured at a variety of intensities up to 120
dB from background noise (BN) .
Munc18-1 Expression Is Not Altered
in α -Neurexin HET Mice
Summary
• Our findings demonstrate that the heterozygous
loss of α-neurexin I and α-neurexin II in mice
leads to phenotypes relevant to autism and
schizophrenia.
• However, the link between neurexin deficiency
and the manifestation of psychiatric disorders
remain unclear.
11 4-16

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11 4-16

  • 1. Heterozygous Deletion of α -Neurexin I or α -Neurexin II Results in Behaviors Relevant to Autism and Schizophrenia Presented by Muhammad Younis
  • 2. Background • Schizophrenia is a mental disorder characterized by abnormal social behavior and failure to understand reality. • Autism is a neurodevelopmental disorder characterized by impaired social interaction. • Human genetic studies have found heterozygous deletions affecting NRXN1 and NRXN2, encoding - neurexin I (Nrxn1) and -neurexin II (Nrxn2), in individuals with autism spectrum disorders and schizophrenia.
  • 3. α -Neurexin HET Mice Have Altered Social Behaviors HET= Heterozygous deletion of Nrxn1α or Nrxn2α
  • 4. α -Neurexin HET Mice Show Limited Impairments in Cognition Passive avoidance testDiscrimination memory
  • 5. α -Neurexin HET Mice Have Unaltered Ambulation and Anxiety
  • 6. Nrxn HET mice do not display anxiety like behaviors Plus maze
  • 7. α -Neurexin HET Mice Show Intact Prepulse Inhibition • Prepulse inhibition of startle are operational measures of sensory gating. • Sensory gating is disrupted in schizophrenia, • Acoustic startle reactivity was measured at a variety of intensities up to 120 dB from background noise (BN) .
  • 8. Munc18-1 Expression Is Not Altered in α -Neurexin HET Mice
  • 9. Summary • Our findings demonstrate that the heterozygous loss of α-neurexin I and α-neurexin II in mice leads to phenotypes relevant to autism and schizophrenia. • However, the link between neurexin deficiency and the manifestation of psychiatric disorders remain unclear.