ABSTRACT
Pou3f2/Brn2 is a transcription factor that helps to determine the cellular identity of neocortical or hypothalamic neurons. Mammalian Pou3f2 contains three homopolymeric amino acids that are not present in amphibian Pou3f2. These amino acids contribute to monoamine function, which may play specific roles in mammalian development and behavior. Previous work has indicated that Pou3f2â¿ mice, which lack the homopolymeric amino acids, exhibited declined maternal activity and impaired object and spatial recognition. The current study, analyzed weight gain, brain development, home cage activity, social interaction, and response to novel objects in Pou3f2â¿ mice to determine which aspects of behavior were affected by monoamine dysregulation. Compared to their wild type counterparts, Pou3f2â¿ mice showed decreased social interaction and reduced home cage activity during their active phase. However, they showed normal weight gain, brain development, and responses to novelty. These results indicate that monoamine dysregulation in Pou3f2â¿ mice may specifically affect basal activity and social development, without altering non-social motivation.
Subject(s)
Behavior, Animal/physiology , Nerve Tissue Proteins/physiology , POU Domain Factors/physiology , Social Behavior , Animals , Biogenic Monoamines/physiology , Brain/growth & development , Exploratory Behavior/physiology , Hypothalamus/physiology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neocortex/physiology , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/genetics , Neurons/physiology , POU Domain Factors/chemistry , POU Domain Factors/genetics , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Weight GainABSTRACT
Sequence comparison of Hoxd-13 among vertebrates revealed the presence of taxon-specific polyalanine tracts in amniotes. To investigate their function at the organismal level, we replaced the wild-type Hoxd-13 gene with one lacking the 15-residue polyalanine tract by using homologous recombination. Sesamoid bone formation in knock-in mice was different from that in the wild type; this was observed not only in the homozygotes but also in the heterozygotes. The present study provides the first direct evidence that taxon-specific homopolymeric amino acid repeats are involved in phenotypic diversification at the organismal level.
