Deficient maternal behavior in multiparous Pou3f2⊿ mice is associated with an impaired exploratory activity.

Mammalian adult females develop specialized body parts, namely mammary glands and uterus, and exhibit specialized maternal behavior, lactation/nursing and care for their offspring. As the brain plays an essential role in regulating related physiological functions in the body, the morphology or function of the mammalian brain has been modified to manage newly equipped structures and functions. However, this evolutionary process is largely unknown. Pou3f2/Brn2 is an evolutionarily remarkable gene as it contains mammal-specific base sequences encoding three stretches of homopolymeric amino acids (polyAAs): poly-glycine (polyG), poly-glutamine (polyQ), and poly-proline (polyP). Previously, we demonstrated that POU3F2 acquisition of mammal-specific polyAAs contributed to the establishment of behaviors characteristic of mammals. Here, we demonstrated that Pou3f2⊿ mice displayed basic features required for maternal care. However, Pou3f2⊿ mice exhibited deficits in the reproductive performance and maternal behavior, which were not fully improved by multiparas. Therefore, we extensively investigated pup retrieval behavior and discovered that the retrieval and the exploratory behaviors were impaired in Pou3f2⊿ female mice, but not in males. Altogether, our data suggest that POU3F2 acquisition of mammal-specific polyAAs contributes to the continuous awareness and curiosity needed for maternal interaction.