Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice

Kathryn K. Chadman, Shiaoching Gong, Maria L. Scattoni, Sarah E. Boltuck, Shruti U. Gandhy, Nathaniel Heintz, Jacqueline Crawley

Research output: Contribution to journalArticle

187 Citations (Scopus)

Abstract

Neuroligin-3 is a member of the class of cell adhesion proteins that mediate synapse development and have been implicated in autism. Mice with the human R451C mutation (NL3), identical to the point mutation found in two brothers with autism spectrum disorders, were generated and phenotyped in multiple behavioral assays with face validity to the diagnostic symptoms of autism. No differences between NL3 and their wildtype (WT) littermate controls were detected on measures of juvenile reciprocal social interaction, adult social approach, cognitive abilities, and resistance to change in a spatial habit, findings which were replicated in several cohorts of males and females. Physical and procedural abilities were similar across genotypes on measures of general health, sensory abilities, sensorimotor gating, motor functions, and anxiety-related traits. Minor developmental differences were detected between NL3 and WT, including slightly different rates of somatic growth, slower righting reflexes at postnatal days 2-6, faster homing reflexes in females, and less vocalizations on postnatal day 8 in males. Significant differences in NL3 adults included somewhat longer latencies to fall from the rotarod, less vertical activity in the open field, and less acoustic startle to high decibel tones. The humanized R451C mutation in mice did not result in apparent autism-like phenotypes, but produced detectable functional consequences that may be interpreted in terms of physical development and/or reduced sensitivity to stimuli.

Original languageEnglish (US)
Pages (from-to)147-158
Number of pages12
JournalAutism Research
Volume1
Issue number3
DOIs
StatePublished - 2008
Externally publishedYes

Fingerprint

Aptitude
Autistic Disorder
Phenotype
Sensory Gating
Righting Reflex
Mutation
Interpersonal Relations
Point Mutation
Acoustics
Reproducibility of Results
Cell Adhesion
Synapses
Habits
Reflex
Siblings
Anxiety
Genotype
Health
Growth
neuroligin 3

Keywords

  • Autism
  • Behavior phenotyping
  • Mouse model
  • Neuroligin
  • Social behavior

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Genetics(clinical)
  • Medicine(all)

Cite this

Chadman, K. K., Gong, S., Scattoni, M. L., Boltuck, S. E., Gandhy, S. U., Heintz, N., & Crawley, J. (2008). Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice. Autism Research, 1(3), 147-158. https://doi.org/10.1002/aur.22

Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice. / Chadman, Kathryn K.; Gong, Shiaoching; Scattoni, Maria L.; Boltuck, Sarah E.; Gandhy, Shruti U.; Heintz, Nathaniel; Crawley, Jacqueline.

In: Autism Research, Vol. 1, No. 3, 2008, p. 147-158.

Research output: Contribution to journalArticle

Chadman, KK, Gong, S, Scattoni, ML, Boltuck, SE, Gandhy, SU, Heintz, N & Crawley, J 2008, 'Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice', Autism Research, vol. 1, no. 3, pp. 147-158. https://doi.org/10.1002/aur.22
Chadman KK, Gong S, Scattoni ML, Boltuck SE, Gandhy SU, Heintz N et al. Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice. Autism Research. 2008;1(3):147-158. https://doi.org/10.1002/aur.22
Chadman, Kathryn K. ; Gong, Shiaoching ; Scattoni, Maria L. ; Boltuck, Sarah E. ; Gandhy, Shruti U. ; Heintz, Nathaniel ; Crawley, Jacqueline. / Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice. In: Autism Research. 2008 ; Vol. 1, No. 3. pp. 147-158.
@article{96377c3cc8364c118c61db539a1bca83,
title = "Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice",
abstract = "Neuroligin-3 is a member of the class of cell adhesion proteins that mediate synapse development and have been implicated in autism. Mice with the human R451C mutation (NL3), identical to the point mutation found in two brothers with autism spectrum disorders, were generated and phenotyped in multiple behavioral assays with face validity to the diagnostic symptoms of autism. No differences between NL3 and their wildtype (WT) littermate controls were detected on measures of juvenile reciprocal social interaction, adult social approach, cognitive abilities, and resistance to change in a spatial habit, findings which were replicated in several cohorts of males and females. Physical and procedural abilities were similar across genotypes on measures of general health, sensory abilities, sensorimotor gating, motor functions, and anxiety-related traits. Minor developmental differences were detected between NL3 and WT, including slightly different rates of somatic growth, slower righting reflexes at postnatal days 2-6, faster homing reflexes in females, and less vocalizations on postnatal day 8 in males. Significant differences in NL3 adults included somewhat longer latencies to fall from the rotarod, less vertical activity in the open field, and less acoustic startle to high decibel tones. The humanized R451C mutation in mice did not result in apparent autism-like phenotypes, but produced detectable functional consequences that may be interpreted in terms of physical development and/or reduced sensitivity to stimuli.",
keywords = "Autism, Behavior phenotyping, Mouse model, Neuroligin, Social behavior",
author = "Chadman, {Kathryn K.} and Shiaoching Gong and Scattoni, {Maria L.} and Boltuck, {Sarah E.} and Gandhy, {Shruti U.} and Nathaniel Heintz and Jacqueline Crawley",
year = "2008",
doi = "10.1002/aur.22",
language = "English (US)",
volume = "1",
pages = "147--158",
journal = "Autism Research",
issn = "1939-3806",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice

AU - Chadman, Kathryn K.

AU - Gong, Shiaoching

AU - Scattoni, Maria L.

AU - Boltuck, Sarah E.

AU - Gandhy, Shruti U.

AU - Heintz, Nathaniel

AU - Crawley, Jacqueline

PY - 2008

Y1 - 2008

N2 - Neuroligin-3 is a member of the class of cell adhesion proteins that mediate synapse development and have been implicated in autism. Mice with the human R451C mutation (NL3), identical to the point mutation found in two brothers with autism spectrum disorders, were generated and phenotyped in multiple behavioral assays with face validity to the diagnostic symptoms of autism. No differences between NL3 and their wildtype (WT) littermate controls were detected on measures of juvenile reciprocal social interaction, adult social approach, cognitive abilities, and resistance to change in a spatial habit, findings which were replicated in several cohorts of males and females. Physical and procedural abilities were similar across genotypes on measures of general health, sensory abilities, sensorimotor gating, motor functions, and anxiety-related traits. Minor developmental differences were detected between NL3 and WT, including slightly different rates of somatic growth, slower righting reflexes at postnatal days 2-6, faster homing reflexes in females, and less vocalizations on postnatal day 8 in males. Significant differences in NL3 adults included somewhat longer latencies to fall from the rotarod, less vertical activity in the open field, and less acoustic startle to high decibel tones. The humanized R451C mutation in mice did not result in apparent autism-like phenotypes, but produced detectable functional consequences that may be interpreted in terms of physical development and/or reduced sensitivity to stimuli.

AB - Neuroligin-3 is a member of the class of cell adhesion proteins that mediate synapse development and have been implicated in autism. Mice with the human R451C mutation (NL3), identical to the point mutation found in two brothers with autism spectrum disorders, were generated and phenotyped in multiple behavioral assays with face validity to the diagnostic symptoms of autism. No differences between NL3 and their wildtype (WT) littermate controls were detected on measures of juvenile reciprocal social interaction, adult social approach, cognitive abilities, and resistance to change in a spatial habit, findings which were replicated in several cohorts of males and females. Physical and procedural abilities were similar across genotypes on measures of general health, sensory abilities, sensorimotor gating, motor functions, and anxiety-related traits. Minor developmental differences were detected between NL3 and WT, including slightly different rates of somatic growth, slower righting reflexes at postnatal days 2-6, faster homing reflexes in females, and less vocalizations on postnatal day 8 in males. Significant differences in NL3 adults included somewhat longer latencies to fall from the rotarod, less vertical activity in the open field, and less acoustic startle to high decibel tones. The humanized R451C mutation in mice did not result in apparent autism-like phenotypes, but produced detectable functional consequences that may be interpreted in terms of physical development and/or reduced sensitivity to stimuli.

KW - Autism

KW - Behavior phenotyping

KW - Mouse model

KW - Neuroligin

KW - Social behavior

UR - http://www.scopus.com/inward/record.url?scp=64849084164&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=64849084164&partnerID=8YFLogxK

U2 - 10.1002/aur.22

DO - 10.1002/aur.22

M3 - Article

C2 - 19360662

AN - SCOPUS:64849084164

VL - 1

SP - 147

EP - 158

JO - Autism Research

JF - Autism Research

SN - 1939-3806

IS - 3

ER -