The winged helix gene, Mf3, is required for normal development of the diencephalon and midbrain, postnatal growth and the milk-ejection reflex.

Labosky PA, Winnier GE, Jetton TL, Hargett L, Ryan AK, Rosenfeld MG, Parlow AF, Hogan BL
Development. 1997 124 (7): 1263-74

PMID: 9118797

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 neurectoderm 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 bodies, the posterior-most part of the hypothalamus. Mice homozygous for a deletion of the mf3 locus on a [129 x Black Swiss] background display variable phenotypes consistent with a requirement for the gene at several stages of embryonic and postnatal development. Approximately six percent of the mf3-/- embryos show an open neural tube in the diencephalon and midbrain region, and another five percent show a severe reduction of the posterior body axis; both these classes of affected embryos die in utero. Surviving homozygotes have an apparently normal phenotype 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. Although much smaller than normal, the mice are fertile. However, mf3-/- females 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 hypothalamus development and suggest that Mf3 may play a role in postnatal growth and lactation.

MeSH Terms (28)

Animals Behavior, Animal Body Patterning Brain Chimera Crosses, Genetic Diencephalon DNA-Binding Proteins Female Forkhead Transcription Factors Heterozygote Hindlimb Homozygote Hypothalamus Immunohistochemistry Male Mammary Glands, Animal Mesencephalon Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Mutant Strains Milk Ejection Phenotype Pituitary Gland Radioimmunoassay Reflex Transcription Factors

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