Deficiency in Mouse Oxytocin Prevents Milk Ejection,but not Fertility or Parturition

Abstract

Oxytocin is a nonapeptide hormone that participates in the regulation of parturition and lactation. It has also been implicated in various behaviors, such as mating and maternal, and memory. To investigate whether or not oxytocin (OT) is essential for any of these functions, we eliminated, by homologous recombination, most of the first intron and the last two exons of the OT gene in mice. Those exons encode the neurophysin portion of the oxytocin preprohormone which is hypothesized to help in the packaging and transport of OT. The homozygous mutant mice have no detectable neurophysin or processed oxytocin in the paraventricular nucleus, supraoptic nucleus or posterior pituitary. Interestingly, homozygous mutant males and females are fertile and the homozygous mutant females are able to deliver their litters. However, the pups do not successfully suckle and die within 24 h without milk in their stomachs. OT injection into the dams restores the milk injection in response to suckling. These results indicate an absolute requirement for oxytocin for successful milk injection, but not for mating, parturition and milk production, in mice.

Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice

“…This contradiction might be caused by differences in the targeting construct used, which resulted in the elimination of the majority of the Neurophysin but not the OXT coding region of the Oxt gene, or in the testing paradigm used (9,27). In the study reporting decreased duration of aggressive attack, the tests were performed in a neutral arena, although in our study and in those of others reporting increased aggression (16,28), a resident intruder paradigm was used.…”

“…OXT-deficient (Oxt Ϫ/Ϫ ) mice displayed impairments in milk ejection (8,9) and social recognition (10) but no obvious defects in parturition (8,9). Although OXT is a strong uterotonin and is considered to drive parturition, the previous observations unexpectedly and clearly prove that OXT is not essential for labor in mice.…”

Mammary-derived signals activate programmed cell death during the first stage of mammary gland involution

“…These mice contain a homozygous deletion of the oxytocin gene (15). Milk is retained in the alveolar lumens of these mice due to failure of milk ejection.…”

“…In the third model, milk ejection was impaired due to oxytocin deficiency (oxy Ϫ͞Ϫ mice). The oxy Ϫ͞Ϫ mice carry a homozygous targeted disruption of the oxytocin gene and can breed normally, but there is no lactation due to failure of milk ejection (15). Another lactation failure model [whey acidic protein-simian virus 40 T antigen (WAP-TAg) transgenic mice] showed that lactogenic hormones can preserve lobular-alveolar structure even in the presence of extensive PCD.…”

Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice

“…32 Mice were backcrossed 10 generations into a C57BL/6J background; 22 Oxt þ / þ mice (12 males and 10 females) and 18 OxtÀ/À mice (8 males and 10 females) were used as subjects. All subjects were 2-to 4-month-old littermates generated from heterozygous matings.…”