Publications by authors named "Ailsa Carlisle"

Early nutrition has significant effects on physiological outcomes during adult life. We have analysed the effect of maternal α-casein (CSN1S1) deficiency on the physiological fate of dams and their offspring. α-casein deficiency reduces maternal milk protein concentration by more than 50% and attenuates the growth of pups to 27% (p < 0.

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Article Synopsis
  • Highly expressed gene loci, like those for casein, are ideal targets for inserting transgenes due to their abundant protein production in mammals, particularly in milk.
  • The α-casein gene was successfully used as a site for transgene insertion in mice, allowing for the expression of an antibody light chain (A1L) that is secreted into milk.
  • While transgene expression in these mice was stable, it was much lower than the native α-casein production, leading to reduced total milk protein and poor growth in pups fed by homozygous transgenic mothers.
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Goniodysgenesis is a developmental abnormality of the anterior chamber of the eye. It is generally considered to be congenital in dogs (), and has been associated with glaucoma and blindness. Goniodysgenesis and early-onset glaucoma initially emerged in Border Collies in Australia in the late 1990s and have subsequently been found in this breed in Europe and the USA.

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  • The FANTOM5 project mapped transcription initiation events in human and mouse genomes with high precision using CAGE technology and single-molecule sequencing.
  • Over 3,000 diverse samples, including primary cells and tissues, were analyzed through a standardized process starting from RNA quality assessment to generating transcription initiation frequencies.
  • The analysis identified around 200,000 (human) and 150,000 (mouse) non-overlapping peaks, enabling the annotation of both known and novel promoters and providing insights into transcriptional regulation in different cellular states.
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MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species.

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Objectives: Early malnutrition is a highly prevalent condition in developing countries. Different rodent models of postnatal early malnutrition have been used to approach the subject experimentally, inducing early malnutrition by maternal malnutrition, temporal maternal separation, manipulation of litter size or the surgical nipple ligation to impair lactation. Studies on the behaviour of (previously) malnourished animals using animal models have produced sometimes contradictory results regarding the effects of early postnatal malnutrition and have been criticized for introducing potential confounding factors.

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Development of the mammary gland requires the coordinated action of proteolytic enzymes during two phases of remodelling. Firstly, new ducts and side-branches thereof need to be established during pregnancy to generate an extensive ductal tree allowing the secretion and transport of milk. A second wave of remodelling occurs during mammary involution after weaning.

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Since large animal transgenesis has been successfully attempted for the first time about 25 years ago, the technology has been applied in various lines of transgenic pigs. Nevertheless one of the concerns with the technology--animal welfare--has not been approached through systematic assessment and statements regarding the welfare of transgenic pigs have been based on anecdotal observations during early stages of transgenic programs. The main aim of the present study was therefore to perform an extensive welfare assessment comparing heterozygous transgenic animals expressing GFP with wildtype animals along various stages of post natal development.

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The major physiological function of milk is the transport of amino acids, carbohydrates, lipids and minerals to mammalian offspring. Caseins, the major milk proteins, are secreted in the form of a micelle consisting of protein and calcium-phosphate.We have analysed the role of the milk protein α-casein by inactivating the corresponding gene in mice.

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Lentiviral vectors have recently emerged as an efficient method of transgene delivery to the germline of animals. We now demonstrate that combining this efficiency with embryo splitting procedures enables the production of monozygotic twins, one of which is transgenic. We propose that this approach can be used to generate animals in which cell or tissue transplantation can be achieved without the use of immunosuppressive regimes.

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Progress with techniques using zona-pellucida denuded embryos has resulted in the birth of live cattle, pigs, and mice. The application of zona-free methods in sheep has been restricted to in vitro studies. In this report, we demonstrate that live lambs can be produced from zona-free IVF embryos.

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Traditional methods of transgene delivery in livestock are inefficient. Recently, human immunodeficiency virus (HIV-1) based lentiviral vectors have been shown to offer an efficient transgene delivery system. We now extend this method by demonstrating efficient generation of transgenic pigs using an equine infectious anaemia virus derived vector.

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