Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0004352 (
autism
)
32,579
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Background:
Brinps 1-3
, and Astrotactins (
Astn
)
1 and 2
, are members of the Membrane Attack Complex/Perforin (MACPF) superfamily that are predominantly expressed in the mammalian brain during development. Genetic variation at the human
BRINP2
/ASTN1
and
BRINP1/ASTN2
loci has been implicated in neurodevelopmental disorders. We, and others, have previously shown that
Brinp1
-/-
mice exhibit behavior reminiscent of
autism
spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD).
Method:
We created
Brinp2
-/-
mice and
Brinp3
-/-
mice via the Cre-mediated LoxP system to investigate the effect of gene deletion on anatomy and behavior. Additionally,
Brinp2
-/-
Brinp3
-/-
double knock-out mice were generated by interbreeding
Brinp2
-/-
and
Brinp3
-/-
mice. Genomic validation was carried out for each knock-out line, followed by histological, weight and behavioral examination.
Brinp1
-/-
Brinp2
-/-
Brinp3
-/-
triple knock-out mice were also generated by crossing
Brinp2/3
double knock-out mice with previously generated
Brinp1
-/-
mice, and examined by weight and histological analysis.
Results:
Brinp2
-/-
and
Brinp3
-/-
mice differ in their behavior:
Brinp2
-/-
mice are hyperactive, whereas
Brinp3
-/-
mice exhibit marked changes in anxiety-response on the elevated plus maze.
Brinp3
-/-
mice also show evidence of altered sociability. Both
Brinp2
-/-
and
Brinp3
-/-
mice have normal short-term memory, olfactory responses, pre-pulse inhibition, and motor learning. The double knock-out mice show behaviors of
Brinp2
-/-
and
Brinp3
-/-
mice, without evidence of new or exacerbated phenotypes.
Conclusion:
Brinp3
is important in moderation of anxiety, with potential relevance to anxiety disorders.
Brinp2
dysfunction resulting in hyperactivity may be relevant to the association of ADHD with chromosome locus 1q25.2.
Brinp2
-/-
and
Brinp3
-/-
genes do not compensate in the mammalian brain and likely have distinct molecular or cell-type specific functions.
...
PMID:Mice Lacking
Brinp2
or
Brinp3
, or Both, Exhibit Behaviors Consistent with Neurodevelopmental Disorders. 2782 31
