Deficiency in mouse oxytocin prevents milk ejection, but not fertility or parturition

被引:233
作者
Young, WS
Shepard, E
Amico, J
Hennighausen, L
Wagner, KU
LaMarca, ME
McKinney, C
Ginns, EI
机构
[1] NIMH, CELL BIOL LAB, NATL INST HLTH, BETHESDA, MD 20892 USA
[2] NIMH, CLIN NEUROSCI BRANCH, NATL INST HLTH, BETHESDA, MD 20892 USA
[3] NIDDK, BIOCHEM & METAB LAB, PITTSBURGH, PA 15261 USA
[4] UNIV PITTSBURGH, SCH MED, DIV ENDOCRINOL & METAB, PITTSBURGH, PA 15261 USA
[5] VET ADM MED CTR, PITTSBURGH, PA 15261 USA
关键词
homologous recombination; lactation; mammary gland; reproduction paraventricular; supraoptic;
D O I
10.1046/j.1365-2826.1996.05266.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 ejection in response to suckling. These results indicate an absolute requirement for oxytocin for successful milk ejection, but not for mating, parturition and milk production, in mice.
引用
收藏
页码:847 / 853
页数:7
相关论文
共 63 条
  • [1] AN IMMUNOCHEMICAL ANALYSIS OF OXYTOCIN AND VASOPRESSIN PROHORMONE PROCESSING INVIVO
    ALTSTEIN, M
    WHITNALL, MH
    HOUSE, S
    KEY, S
    GAINER, H
    [J]. PEPTIDES, 1988, 9 (01) : 87 - 105
  • [2] AMICO JA, 1988, INT CONGR SER, V797, P207
  • [3] OXYTOCIN IN HUMAN-PLASMA - CORRELATION WITH NEUROPHYSIN AND STIMULATION WITH ESTROGEN
    AMICO, JA
    SEIF, SM
    ROBINSON, AG
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1981, 52 (05) : 988 - 993
  • [4] A NOVEL OXYTOCIN-LIKE AND VASOTOCIN-LIKE PEPTIDE IN HUMAN-PLASMA AFTER ADMINISTRATION OF ESTROGEN
    AMICO, JA
    ERVIN, MG
    LEAKE, RD
    FISHER, DA
    FINN, FM
    ROBINSON, AG
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1985, 60 (01) : 5 - 12
  • [5] OXYTOCIN ANTAGONISTS DELAY THE INITIATION OF PARTURITION AND PROLONG ITS ACTIVE PHASE IN RATS
    ANTONIJEVIC, IA
    DOUGLAS, AJ
    DYE, S
    BICKNELL, RJ
    LENG, G
    RUSSELL, JA
    [J]. JOURNAL OF ENDOCRINOLOGY, 1995, 145 (01) : 97 - 103
  • [6] BARGMANN WOLFGANG, 1951, AMER SCI, V39, P255
  • [7] PHYLOGENETIC CROSS-REACTIVITIES OF MONOCLONAL-ANTIBODIES PRODUCED AGAINST RAT NEUROPHYSIN
    BENBARAK, Y
    RUSSELL, JT
    WHITNALL, M
    OZATO, K
    GAINER, H
    [J]. CELLULAR AND MOLECULAR NEUROBIOLOGY, 1984, 4 (04) : 339 - 349
  • [8] DYNORPHIN-A INHIBITS AND NALOXONE INCREASES THE ELECTRICALLY STIMULATED RELEASE OF OXYTOCIN BUT NOT VASOPRESSIN FROM THE TERMINALS OF THE NEURAL LOBE
    BONDY, CA
    GAINER, H
    RUSSELL, JT
    [J]. ENDOCRINOLOGY, 1988, 122 (04) : 1321 - 1327
  • [9] SYNTHESIS, TRANSPORT, AND RELEASE OF POSTERIOR PITUITARY-HORMONES
    BROWNSTEIN, MJ
    RUSSELL, JT
    GAINER, H
    [J]. SCIENCE, 1980, 207 (4429) : 373 - 378
  • [10] SYNTHESIS OF OXYTOCIN IN AMNION, CHORION, AND DECIDUA MAY INFLUENCE THE TIMING OF HUMAN PARTURITION
    CHIBBAR, R
    MILLER, FD
    MITCHELL, BF
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1993, 91 (01) : 185 - 192