Phenotypes Associated with This Genotype

Genotype
MGI:3045634

• Allelic Composition: Htr1a^tm1Toth/Htr1a^tm1Toth
• Genetic Background: involves: 129P2/OlaHsd * Black Swiss

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:66581 )

• homozygotes show increased limbic excitability and seizure susceptibility (i.e. lower seizure threshold and higher lethality) in response to kainic acid administration

abnormal spatial learning ( J:66581 )

• homozygotes show impaired hippocampal-dependent spatial learning and memory tasks in the hidden platform (spatial) version of the Morris water-maze and the delayed version of the Y-maze

• in contrast, they display normal learning and memory in non-hippocampal tasks, such as the visible platform (nonspatial) version of the water-maze, the immediate version of the Y-maze, and the spontaneous-alternation test of working memory

• motor behavior and motivation to perform tasks appear unaffected

increased anxiety-related response ( J:49752 , J:61579 )

• homozygotes are viable and developmentally normal but avoid a novel and fearful environment and vigorously attempt to escape stressful situations (J:49752)

• although both male and female mutants show increased anxiety and stress response, anxiety is less prominent in female mice (J:49752)

• homozygotes are insensitive to the anxiolytic effect of diazepam, a classical benzodiazepine, in the elevated-plus maze and in the open-field test of anxiety (J:61579)

• consistent with "BZ-resistant anxiety", binding of both BZ and non-BZ GABAA receptor ligands are reduced (J:61579)

• in homozygotes, binding of the BZ-specific ligand methyl-3H-flunitrazepam is reduced ~16% in amygdala and 8% in cortex (J:61579)

increased locomotor activity ( J:49752 )

• mutant females, but not males, show increased locomotor activity in the open-field test

• both males and females show increased mobility in the forced swim test; no gender differences are observed in this test

nervous system

increased susceptibility to pharmacologically induced seizures ( J:66581 )

• homozygotes show increased limbic excitability and seizure susceptibility (i.e. lower seizure threshold and higher lethality) in response to kainic acid administration

decreased paired-pulse facilitation ( J:61579 , J:66581 )

• homozygotes display impaired paired-pulse inhibition in the CA1 region of the hippocampus, indicating reduced GABAergic inhibition (J:61579)

• homozygotes show specific alterations in GABAA receptor subunit levels in the amygdala, cortex and hippocampus (J:61579)

• electrophysiological data show absence of paired-pulse facilitation in the dentate gyrus of homozygous mutants (J:66581)

• the lack of paired-pulse inhibition in the CA1 region of the hippocampus indicates a defect in short-term neuroplasticity (J:66581)

• in contrast, homozygotes show no abnormality in long-term plasticity, at least in the CA1 region of the hippocampus (J:66581)