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

Michael P. McDonald, Rosemary Wong, Gregory Goldstein, Bruce Weintraub, Sheue Yann Cheng, Jacqueline 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 - 1998
Externally publishedYes

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

McDonald, M. P., Wong, R., Goldstein, G., Weintraub, B., Cheng, S. Y., & Crawley, J. (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 P.; Wong, Rosemary; Goldstein, Gregory; Weintraub, Bruce; Cheng, Sheue Yann; Crawley, Jacqueline.

In: Learning and Memory, Vol. 5, No. 4-5, 1998, p. 289-301.

Research output: Contribution to journalArticle

McDonald, MP, Wong, R, Goldstein, G, Weintraub, B, Cheng, SY & Crawley, J 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 P. ; Wong, Rosemary ; Goldstein, Gregory ; Weintraub, Bruce ; Cheng, Sheue Yann ; Crawley, Jacqueline. / 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.
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