60 research outputs found

    Biological control of rodents - the case for fertility control using immunocontraception

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    Marsupial tammar wallaby delivers milk bioactives to altricial pouch young to support lung development

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    Our research is exploiting the marsupial as a model to understand the signals required for lung development. Marsupials have a unique reproductive strategy, the mother gives birth to altricial neonate with an immature lung and the changes in milk composition during lactation in marsupials appears to provide bioactives that can regulate diverse aspects of lung development, including branching morphogenesis, cell proliferation and cell differentiation. These effects are seen with milk collected between 25 and 100days postpartum. To better understand the temporal effects of milk composition on postnatal lung development we used a cross-fostering technique to restrict the tammar pouch young to milk composition not extending beyond day 25 for 45days of its early postnatal life. These particular time points were selected as our previous study showed that milk protein collected prior to ~day 25 had no developmental effect on mouse embryonic lungs in culture. The comparative analysis of the foster group and control young at day 45 postpartum demonstrated that foster pouch young had significantly reduced lung size. The lungs in fostered young were comprised of large intermediate tissue, had a reduced size of airway lumen and a higher percentage of parenchymal tissue. In addition, expression of marker genes for lung development (BMP4, WNT11, AQP-4, HOPX and SPB) were significantly reduced in lungs from fostered young. Further, to identify the potential bioactive expressed by mammary gland that may have developmental effect on pouch young lungs, we performed proteomics analysis on tammar milk through mass-spectrometry and listed the potential bioactives (PDGF, IGFBP5, IGFBPL1 and EGFL6) secreted in milk that may be involved in regulating pouch young lung development. The data suggest that postnatal lung development in the tammar young is most likely regulated by maternal signalling factors supplied through milk

    The tammar wallaby: a marsupial model to examine the timed delivery and role of bioactives in milk

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    It is now clear that milk has multiple functions; it provides the most appropriate nutrition for growth of the newborn, it delivers a range of bioactives with the potential to stimulate development of the young, it has the capacity to remodel the mammary gland (stimulate growth or signal cell death) and finally milk can provide protection from infection and inflammation when the mammary gland is susceptible to these challenges. There is increasing evidence to support studies using an Australian marsupial, the tammar wallaby (Macropus eugenii), as an interesting and unique model to study milk bioactives. Reproduction in the tammar wallaby is characterized by a short gestation, birth of immature young and a long lactation. All the major milk constituents change substantially and progressively during lactation and these changes have been shown to regulate growth and development of the tammar pouch young and to have roles in mammary gland biology. This review will focus on recent reports examining the control of lactation in the tammar wallaby and the timed delivery of milk bioactivity

    A bipedal mammalian model for spinal cord injury research: The tammar wallaby [version 1; referees: 2 approved]

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    Background: Most animal studies of spinal cord injury are conducted in quadrupeds, usually rodents. It is unclear to what extent functional results from such studies can be translated to bipedal species such as humans because bipedal and quadrupedal locomotion involve very different patterns of spinal control of muscle coordination. Bipedalism requires upright trunk stability and coordinated postural muscle control; it has been suggested that peripheral sensory input is less important in humans than quadrupeds for recovery of locomotion following spinal injury. Methods: We used an Australian macropod marsupial, the tammar wallaby (Macropus eugenii), because tammars exhibit an upright trunk posture, human-like alternating hindlimb movement when swimming and bipedal over-ground locomotion. Regulation of their muscle movements is more similar to humans than quadrupeds. At different postnatal (P) days (P7–60) tammars received a complete mid-thoracic spinal cord transection. Morphological repair, as well as functional use of hind limbs, was studied up to the time of their pouch exit. Results: Growth of axons across the lesion restored supraspinal innervation in animals injured up to 3 weeks of age but not in animals injured after 6 weeks of age. At initial pouch exit (P180), the young injured at P7-21 were able to hop on their hind limbs similar to age-matched controls and to swim albeit with a different stroke. Those animals injured at P40-45 appeared to be incapable of normal use of hind limbs even while still in the pouch. Conclusions: Data indicate that the characteristic over-ground locomotion of tammars provides a model in which regrowth of supraspinal connections across the site of injury can be studied in a bipedal animal. Forelimb weight-bearing motion and peripheral sensory input appear not to compensate for lack of hindlimb control, as occurs in quadrupeds. Tammars may be a more appropriate model for studies of therapeutic interventions relevant to humans

    Immunocontraception of Small Mammals: Case Study for the Wild House Mouse in Australia

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    Many exotic vertebrate species have been introduced either accidentally or intentionally into the Australian environment. Native species have also become pests due to changes in landscape use. Management of these pest populations, whether introduced or indigenous, is of concern both nationally and internationally. Public approval of existing pest control techniques involving lethal agents (poisoning, shooting, trapping, or disease) has declined in favour of alternative techniques, which are more humane, cost effective, species-specific, environmentally friendly, and suitable for delivery on a continental scale. Population management through disruption of reproduction rather than through the use of mortality agents has gained acceptance in the past 10-15 years. This has led to considerable research into the development of immunocontraceptive agents, for example to prevent mouse populations irrupting to plague proportions in cereal-growing regions of Australia. We have examined whether mouse populations can be managed with fertility control delivered using a transmissible mouse-specific virus (mouse cytomegalovirus, MCMV), engineered to carry an infertility agent. Field and laboratory results, as well as computer modelling, show excellent prospects for the use of vaccines based on MCMV. However, the efficiency of transmission of infertility remains a major challenge for the current research program. The public acceptability of the technology is yet to be confirmed. The issues of species specificity, delivery system stability, transmission efficiency, and other potential or perceived risks require open and wide-ranging debate, nationally and internationally, before trial field experiments of a genetically modified virus for controlling field populations of mammals could occur

    Parenteral administration of GnRH constructs and adjuvants: Immuneresponses and effects on reproductive tissues of male mice

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    Two gonadotrophin releasing hormone (GnRH) constructs prepared by either chemical conjugation tokeyhole limpet hemocyanin (GnRH-KLH) or as an expressed recombinant fusion protein (Multimer) wereevaluated with or without adjuvants (immunostimulating complexes, ISCOMs, or cytosine-phosphate-guanosine oligodeoxynucleotides, CpG ODNs). After subcutaneous administration to Balb/c male mice atWeeks 0, 2 and 4, these preparations were assessed for induction of immune responses and effects onreproductive organs. GnRH-KLH plus ISCOMs formulation induced strong IgG immune responses fromWeek 4 through Week 12 resulting in consistent reproductive organ atrophy by Week 12 after sub-cutaneous administration. GnRH-KLH plus CpG ODNs generated immune responses but no atrophy ofreproductive tissues by Week 12. Multimer plus ISCOMs induced poor immune responses and no effectson reproductive tissues by Week 12. In the absence of additional adjuvant, none of the GnRH constructsinduced reproductive organ atrophy. GnRH-KLH induced stronger immune responses when formulatedwith ISCOMs or CpG ODN compared to Multimer. GnRH-KLH with ISCOMs could be an effective colloidalalternative for emulsion GnRH vaccine formulations
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