A bovine oxytocin transgene in mice: expression in the female reproductive organs and regulation during pregnancy, parturition and lactation

Ho, Mei-Yin; Murphy, David

doi:10.1016/s0303-7207(97)00208-6

Cited by 10 publications

(6 citation statements)

References 22 publications

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“…In particular, we have characterized lactation failure in transgenic mice that express activated myr-Akt1 in the mammary gland [25]; prominent CLDs are apparent following parturition, suggesting that secretory activation has not occurred. The presence of large CDLs post-partum is also noted in the following genetically engineered mice: Src null mice (MM Richert and SM Anderson, unpublished data); WAP-human protein C [26]; bovine oxytocin transgenic [27]; oxytocin knockout mice [28]; α-lactalbumin knockout mice [29]; butyrophilin knockout mice [30]; and the xanthine oxidoreductase heterozygous knockout mice [31]. …”

Section: Morphological Differentiation Of the Murine Mammary Glandmentioning

confidence: 99%

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et al. 2007

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The transition from pregnancy to lactation is a critical event in the survival of the newborn since all the nutrient requirements of the infant are provided by milk. While milk contains numerous components, including proteins, that aid in maintaining the health of the infant, lactose and milk fat represent the critical energy providing elements of milk. Much of the research to date on mammary epithelial differentiation has focused upon expression of milk protein genes, providing a somewhat distorted view of alveolar differentiation and secretory activation. While expression of milk protein genes increases during pregnancy and at secretory activation, the genes whose expression is more tightly regulated at this transition are those that regulate lipid biosynthesis. The sterol regulatory element binding protein (SREBP) family of transcription factors is recognized as regulating fatty acid and cholesterol biosynthesis. We propose that SREBP1 is a critical regulator of secretory activation with regard to lipid biosynthesis, in a manner that responds to diet, and that the serine/threonine protein kinase Akt influences this process, resulting in a highly efficient lipid synthetic organ that is able to support the nutritional needs of the newborn.

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Section: Morphological Differentiation Of the Murine Mammary Glandmentioning

confidence: 99%

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et al. 2007

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“…For example, most transgenic mice expressing a bovine oxytocin gene (bOT3.5) ( Fig. 2) fail to deliver normally (110). High levels of transgene RNA were found in the ovary at the end of gestation and at the beginning of lactation in bOT3.5 mice.…”

Section: Oxytocin Physiologymentioning

confidence: 99%

In Vivo Gene Transfer Studies on the Regulation and Function of the Vasopressin and Oxytocin Genes

Murphy

Wells

2003

J Neuroendocrinology

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Novel genes can be introduced into the germline of rats and mice by microinjecting fertilized one-cell eggs with fragments of cloned DNA. A gene sequence can thus be studied within the physiological integrity of the resulting transgenic animals, without any prior knowledge of its regulation and function. These technologies have been used to elucidate the mechanisms by which the expression of the two genes in the locus that codes for the neuropeptides vasopressin and oxytocin is confined to, and regulated physiologically within, specific groups of neurones in the hypothalamus. A number of groups have described transgenes, derived from racine, murine and bovine sources, in both rat and mouse hosts, that mimic the appropriate expression of the endogenous vasopressin and genes in magnocellular neurones (MCNs) of the supraoptic and paraventricular nuclei. However, despite considerable effort, a full description of the cis-acting sequences mediating the regulation of the vasopressin-oxytocin locus remains elusive. Two general conclusions have nonetheless been reached. First, that the proximal promoters of both genes are unable to confer any cell-specific regulatory controls. Second, that sequences downstream of the promoter, within the structural gene and/or the intergenic region that separates the two genes, are crucial for appropriate expression. Despite these limitations, sufficient knowledge has been garnered to specifically direct the expression of reporter genes to vasopressin and oxytocin MCNs. Further, it has been shown that reporter proteins can be directed to the regulated secretory pathway, from where they are subject to appropriate physiological release. The use of MCN expression vectors will thus enable the study of the physiology of these neurones through the targeted expression of biologically active molecules. However, the germline transgenic approach has a number of limitations involving the interpretation of phenotypes, as well as the large cost, labour and time demands. High-throughput somatic gene transfer techniques, principally involving the stereotaxic injection of hypothalamic neuronal groups with replication-deficient adenoviral vectors, are now being developed that obviate these difficulties, and which enable the robust, long-lasting expression of biologically active proteins in vasopressin and oxytocin MCNs.'Neurobiology still has a long way to go to contend with consciousness. Perhaps we should be content to work instead on unconsciousness for a while, and find out about all those processes going on in our brains that we don't know about directly and need science to tell us the answers' (Sydney Brenner) (1).In vivo gene transfer (transgenic) techniques enable the study of any gene sequence within the physiological and developmental integrity of the whole animal. In this review, we describe the work of a number of laboratories, including our own, on the application of transgenesis to the study of the regulation and function of the neurones of the hypothalamic-neurohypophysial system ...

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“…IL-17s are important cytokines for protecting against infection and intestinal mucosal inflammation [ 33 ]. In addition, it has been shown previously that disruption of the bovine OXT and vasopressin pathways results in severe pathology at parturition that can finally lead to maternal death [ 34 ]. This finding is in accordance with the results from the phenotypic analysis, in which cow MORT was highest during the first month after calving.…”

Section: Resultsmentioning

confidence: 99%

“…The bovine OXT plays an essential role in maternal lactation, but apparently also in parturition. The disruption of the bovine OXT in the transgenic mouse model resulted in severe pathology at parturition [ 34 ], suggesting a possible role in the increased MORT at early lactation which was observed. In addition to the function of OXT in parturition, previously, AVP and OXT were shown to each have a role in regulating postpartum estrous behavior in dairy cows, and possibly to be involved in the calving interval and timing of the first insemination postpartum [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic and Genomic Analysis of Cow Mortality in the Israeli Holstein Population

Weller

Ezra

Seroussi

et al. 2023

Genes

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“Livability” was defined as the inverse of the probability of death. The objectives of this study were to estimate the heritability, genetic and phenotypic trends for the livability of Israeli Holstein cows; estimate the genetic and environmental correlations between livability and the nine traits included in the Israeli breeding index; estimate the effect of the inclusion of livability in the Israeli breeding index on expected genetic gains; and compute a genome-wide association study (GWAS) for livability. Seven data sets were analyzed. All data were derived from the database of the Israeli dairy cattle herd-book. The mean livability for the complete data set of 523,954 cows born from 2000 through 2016 was 89.6%. Pregnancy reduced livability by 15%. Livability generally increased with parity and days in milk within parity. Heritability of livability was 0.0082. Phenotypic and genetic trends over the 14-year period from 2000 through 2013 were −0.42% and −0.22% per year. If livability is included in the Israeli breeding index, accounting for 9% of the index, livability would increase by 1.3% and protein production would decrease by 11 kg over the next decade, as compared to the current index. A marker in proximity to the oxytocin–vasopressin locus had the greatest effect in the GWAS. Oxytocin activity in cattle affects calving-associated pathologies and maternal death. Inclusion of livability in the Israeli breeding index is not recommended.

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A bovine oxytocin transgene in mice: expression in the female reproductive organs and regulation during pregnancy, parturition and lactation

Cited by 10 publications

References 22 publications

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In Vivo Gene Transfer Studies on the Regulation and Function of the Vasopressin and Oxytocin Genes

Genetic and Genomic Analysis of Cow Mortality in the Israeli Holstein Population

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