THE WINGED HELIX GENE, MF3, IS REQUIRED FOR NORMAL DEVELOPMENT OF THEDIENCEPHALON AND MIDBRAIN, POSTNATAL-GROWTH AND THE MILK-EJECTION REFLEX

The mouse Mf3 gene, also known as Fkh5 and HFH-e5.1, encodes a winged helix/forkhead transcription factor, In the early embryo, transcripts for Mf3 are restricted to the presomitic mesoderm and anterior neurect oderm and mesoderm, By 9.5 days post coitum, expression in the nervous system is predominantly in the diencephalon, midbrain and neural tube . After midgestation, the highest level of mRNA is in the mammillary b odies, the posterior-most part of the hypothalamus. Mice homozygous fo r a deletion of the mf3 locus on a [129 x Black Swiss] background disp lay variable phenotypes consistent with a requirement for the gene at several stages of embryonic and postnatal development, Approximately s ix percent of the mf3-/- embryos show an open neural tube in the dienc ephalon and midbrain region, and another five percent show a severe re duction of the posterior body axis; both these classes of affected emb ryos die in utero, Surviving homozygotes have an apparently normal phe notype at birth. Postnatally, however, mf3-/- pups are severely growth retarded and approximately one third die before weaning, This growth defect is not a direct result of lack of circulating growth hormone or thyrotropin, Mice that survive to weaning are healthy, but they show an abnormal clasping of the hindfeet when suspended by the tail, Altho ugh much smaller than normal, the mice are fertile, However, inf3-/- f emales cannot eject their milk supply to feed their pups. This nursing defect can be corrected with interperitoneal injections of oxytocin, These results provide evidence that Mf3 is required for normal hypotha lamus development and suggest that Mf3 may play a role in postnatal gr owth and lactation.