Mammalian-specific sequences in pou3f2 contribute to maternal behavior.
Various mutations have occurred during evolution among orthologs, genes in different species that diverged from a common ancestral gene by speciation. Here, we report the remarkable deterioration of a characteristic mammalian maternal behavior, pup retrieval, in nonmammalized mice, in which the transcription factor Pou3f2 was replaced with the Xenopus ortholog lacking all of the homopolymeric amino acid repeats of mammalian POU3F2. Most of the pups born to the nonmammalized mice died within days after birth, depending on the dam genotype alone. Quantitative immunohistochemical analysis revealed decreases in the rate-limiting enzymes of dopamine and serotonin synthesis in various brain structures. Similar results were obtained in knock-in mice in which all of the homopolymeric amino acid repeats of mammalian POU3F2 were removed. Pup retrieval behavior in mammals is thus strongly related to monoamine neurotransmitter levels via the acquisition of homopolymeric amino acid repeats during mammalian evolution.
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Japan sutoo@biol.s.u-tokyo.ac.jp sueda@biol.s.u-tokyo.ac.jp.
Makoto
M
Nasu
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Japan sutoo@biol.s.u-tokyo.ac.jp sueda@biol.s.u-tokyo.ac.jp.
Saori
S
Yada
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Japan sutoo@biol.s.u-tokyo.ac.jp sueda@biol.s.u-tokyo.ac.jp.
Atsushi
A
Igarashi
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, JapanInstitute of Medical Science, University of Tsukuba, Japan sutoo@biol.s.u-tokyo.ac.jp sueda@biol.s.u-tokyo.ac.jp.
Den'etsu
D
Sutoo
Institute of Medical Science, University of Tsukuba, Japan.
Kayo
K
Akiyama
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Japan.
Meguru
M
Ito
Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Japan.
Nobuaki
N
Yoshida
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Japan sutoo@biol.s.u-tokyo.ac.jp sueda@biol.s.u-tokyo.ac.jp.
Shintaroh
S
Ueda
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000096:biosynthesis; D005260:Female; D055879:Gene Knock-In Techniques; D008322:Mammals / Q000235:genetics*; D008425:Maternal Behavior / Q000502:physiology*; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D050809:POU Domain Factors / Q000235:genetics* / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D012701:Serotonin / Q000096:biosynthesis; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics
D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; D029867:Xenopus Proteins; C074066:Pou3f2 protein, mouse; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase; D004298:Dopamine
Pou3f2/Brn-2; amino acid repeats; maternal behavior; nonmammalized mice; transcription factor