11 4-16

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Muhammad Younis

Heterozygous Deletion of α -Neurexin I or α -Neurexin II Results in Behaviors Relevant to Autism and Schizophrenia

Science

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.

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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.

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