Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone β1 receptor gene

Michael Mcdonald, Rosemary Wong, Gregory Goldstein, Bruce Weintraub, Sheue Yann Cheng, Jacqueline N. Crawley

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Resistance to thyroid hormone (RTH) is a human syndrome mapped to the thyroid receptor β (TRβ) gene on chromosome 3, representing a mutation of the ligand-binding domain of the TRβ gene. The syndrome is characterized by reduced tissue responsiveness to thyroid hormone and elevated serum levels of thyroid hormones. A common behavioral phenotype associated with RTH is attention deficit hyperactivity disorder (ADHD). To test the hypothesis that RTH produces attention deficits and/or hyperactivity, transgenic mice expressing a mutant TRβ gene were generated. The present experiment tested RTH transgenic mice from the PV kindred on behavioral tasks relevant to the primary features of ADHD: hyperactivity, sustained attention (vigilance), learning, and impulsivity. Male transgenic mice showed elevated locomotor activity in an open field compared to male wild-type littermate controls. Both male and female transgenic mice exhibited impaired learning of an autoshaping task, compared to wild-type controls. On a vigilance task in an operant chamber, there were no differences between transgenics and controls on the proportion of hits, response latency, or duration of stimulus tolerated. On an operant go/no-go task measuring sustained attention and impulsivity, there were no differences between controls and transgenics. These results indicate that transgenic mice bearing a mutant human TRβ gene demonstrate several behavioral characteristics of ADHD and may serve a valuable heuristic role in elucidating possible candidate genes in converging pathways for other causes of ADHD.

Original languageEnglish (US)
Pages (from-to)289-301
Number of pages13
JournalLearning and Memory
Volume5
Issue number4-5
StatePublished - Dec 1 1998

Fingerprint

Thyroid Hormone Receptors
Thyroid Hormone Resistance Syndrome
Transgenic Mice
Attention Deficit Disorder with Hyperactivity
Learning
Thyroid Gland
Impulsive Behavior
Genes
Thyroid Hormones
Chromosomes, Human, Pair 3
Locomotion
Reaction Time
Ligands
Phenotype
Mutation
Serum

All Science Journal Classification (ASJC) codes

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Mcdonald, M., Wong, R., Goldstein, G., Weintraub, B., Cheng, S. Y., & Crawley, J. N. (1998). Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone β1 receptor gene. Learning and Memory, 5(4-5), 289-301.

Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone β1 receptor gene. / Mcdonald, Michael; Wong, Rosemary; Goldstein, Gregory; Weintraub, Bruce; Cheng, Sheue Yann; Crawley, Jacqueline N.

In: Learning and Memory, Vol. 5, No. 4-5, 01.12.1998, p. 289-301.

Research output: Contribution to journalArticle

Mcdonald, M, Wong, R, Goldstein, G, Weintraub, B, Cheng, SY & Crawley, JN 1998, 'Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone β1 receptor gene', Learning and Memory, vol. 5, no. 4-5, pp. 289-301.
Mcdonald, Michael ; Wong, Rosemary ; Goldstein, Gregory ; Weintraub, Bruce ; Cheng, Sheue Yann ; Crawley, Jacqueline N. / Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone β1 receptor gene. In: Learning and Memory. 1998 ; Vol. 5, No. 4-5. pp. 289-301.
@article{29f994cf3c4649c2a9c68cd914d4c776,
title = "Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone β1 receptor gene",
abstract = "Resistance to thyroid hormone (RTH) is a human syndrome mapped to the thyroid receptor β (TRβ) gene on chromosome 3, representing a mutation of the ligand-binding domain of the TRβ gene. The syndrome is characterized by reduced tissue responsiveness to thyroid hormone and elevated serum levels of thyroid hormones. A common behavioral phenotype associated with RTH is attention deficit hyperactivity disorder (ADHD). To test the hypothesis that RTH produces attention deficits and/or hyperactivity, transgenic mice expressing a mutant TRβ gene were generated. The present experiment tested RTH transgenic mice from the PV kindred on behavioral tasks relevant to the primary features of ADHD: hyperactivity, sustained attention (vigilance), learning, and impulsivity. Male transgenic mice showed elevated locomotor activity in an open field compared to male wild-type littermate controls. Both male and female transgenic mice exhibited impaired learning of an autoshaping task, compared to wild-type controls. On a vigilance task in an operant chamber, there were no differences between transgenics and controls on the proportion of hits, response latency, or duration of stimulus tolerated. On an operant go/no-go task measuring sustained attention and impulsivity, there were no differences between controls and transgenics. These results indicate that transgenic mice bearing a mutant human TRβ gene demonstrate several behavioral characteristics of ADHD and may serve a valuable heuristic role in elucidating possible candidate genes in converging pathways for other causes of ADHD.",
author = "Michael Mcdonald and Rosemary Wong and Gregory Goldstein and Bruce Weintraub and Cheng, {Sheue Yann} and Crawley, {Jacqueline N.}",
year = "1998",
month = "12",
day = "1",
language = "English (US)",
volume = "5",
pages = "289--301",
journal = "Learning and Memory",
issn = "1072-0502",
publisher = "Cold Spring Harbor Laboratory Press",
number = "4-5",

}

TY - JOUR

T1 - Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone β1 receptor gene

AU - Mcdonald, Michael

AU - Wong, Rosemary

AU - Goldstein, Gregory

AU - Weintraub, Bruce

AU - Cheng, Sheue Yann

AU - Crawley, Jacqueline N.

PY - 1998/12/1

Y1 - 1998/12/1

N2 - Resistance to thyroid hormone (RTH) is a human syndrome mapped to the thyroid receptor β (TRβ) gene on chromosome 3, representing a mutation of the ligand-binding domain of the TRβ gene. The syndrome is characterized by reduced tissue responsiveness to thyroid hormone and elevated serum levels of thyroid hormones. A common behavioral phenotype associated with RTH is attention deficit hyperactivity disorder (ADHD). To test the hypothesis that RTH produces attention deficits and/or hyperactivity, transgenic mice expressing a mutant TRβ gene were generated. The present experiment tested RTH transgenic mice from the PV kindred on behavioral tasks relevant to the primary features of ADHD: hyperactivity, sustained attention (vigilance), learning, and impulsivity. Male transgenic mice showed elevated locomotor activity in an open field compared to male wild-type littermate controls. Both male and female transgenic mice exhibited impaired learning of an autoshaping task, compared to wild-type controls. On a vigilance task in an operant chamber, there were no differences between transgenics and controls on the proportion of hits, response latency, or duration of stimulus tolerated. On an operant go/no-go task measuring sustained attention and impulsivity, there were no differences between controls and transgenics. These results indicate that transgenic mice bearing a mutant human TRβ gene demonstrate several behavioral characteristics of ADHD and may serve a valuable heuristic role in elucidating possible candidate genes in converging pathways for other causes of ADHD.

AB - Resistance to thyroid hormone (RTH) is a human syndrome mapped to the thyroid receptor β (TRβ) gene on chromosome 3, representing a mutation of the ligand-binding domain of the TRβ gene. The syndrome is characterized by reduced tissue responsiveness to thyroid hormone and elevated serum levels of thyroid hormones. A common behavioral phenotype associated with RTH is attention deficit hyperactivity disorder (ADHD). To test the hypothesis that RTH produces attention deficits and/or hyperactivity, transgenic mice expressing a mutant TRβ gene were generated. The present experiment tested RTH transgenic mice from the PV kindred on behavioral tasks relevant to the primary features of ADHD: hyperactivity, sustained attention (vigilance), learning, and impulsivity. Male transgenic mice showed elevated locomotor activity in an open field compared to male wild-type littermate controls. Both male and female transgenic mice exhibited impaired learning of an autoshaping task, compared to wild-type controls. On a vigilance task in an operant chamber, there were no differences between transgenics and controls on the proportion of hits, response latency, or duration of stimulus tolerated. On an operant go/no-go task measuring sustained attention and impulsivity, there were no differences between controls and transgenics. These results indicate that transgenic mice bearing a mutant human TRβ gene demonstrate several behavioral characteristics of ADHD and may serve a valuable heuristic role in elucidating possible candidate genes in converging pathways for other causes of ADHD.

UR - http://www.scopus.com/inward/record.url?scp=0032458320&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032458320&partnerID=8YFLogxK

M3 - Article

VL - 5

SP - 289

EP - 301

JO - Learning and Memory

JF - Learning and Memory

SN - 1072-0502

IS - 4-5

ER -