Genetics of canine diabetes mellitus part 1: Phenotypes of disease.

This two-part article discusses the mechanisms by which genetic variation can influence the risk of complex diseases, with a focus on canine diabetes mellitus. In Part 1, presented here, the importance of accurate methods for classifying different types of diabetes will be discussed, since this underpins the selection of cases and controls for genetic studies. Part 2 will focus on our current understanding of the genes involved in diabetes risk, and the way in which new genome sequencing technologies are poised to reveal new diabetes genes in veterinary species.

Genetics of canine diabetes mellitus part 2: Current understanding and future directions.

Part 1 of this 2-part review outlined the importance of disease classification in diabetes genetic studies, as well as the ways in which genetic variants may contribute to risk of a complex disease within an individual, or within a particular group of individuals. Part 2, presented here, describes in more detail our current understanding of the genetics of canine diabetes mellitus compared to our knowledge of the human disease. Ongoing work to improve our knowledge, using new technologies, is also introduced.

Evolution of the patella and patelloid in marsupial mammals.

The musculoskeletal system of marsupial mammals has numerous unusual features beyond the pouch and epipubic bones. One example is the widespread absence or reduction (to a fibrous "patelloid") of the patella ("kneecap") sesamoid bone, but prior studies with coarse sampling indicated complex patterns of evolution of this absence or reduction. Here, we conducted an in-depth investigation into the form of the patella of extant marsupial species and used the assembled dataset to reconstruct the likely pattern of evolution of the marsupial patella. Critical assessment of the available literature was followed by examination and imaging of museum specimens, as well as CT scanning and histological examination of dissected wet specimens. Our results, from sampling about 19% of extant marsupial species-level diversity, include new images and descriptions of the fibrocartilaginous patelloid in Thylacinus cynocephalus (the thylacine or "marsupial wolf") and other marsupials as well as the ossified patella in Notoryctes 'marsupial moles', Caenolestes shrew opossums, bandicoots and bilbies. We found novel evidence of an ossified patella in one specimen of Macropus rufogriseus (Bennett's wallaby), with hints of similar variation in other species. It remains uncertain whether such ossifications are ontogenetic variation, unusual individual variation, pathological or otherwise, but future studies must continue to be conscious of variation in metatherian patellar sesamoid morphology. Our evolutionary reconstructions using our assembled data vary, too, depending on the reconstruction algorithm used. A maximum likelihood algorithm favours ancestral fibrocartilaginous "patelloid" for crown clade Marsupialia and independent origins of ossified patellae in extinct sparassodonts, peramelids, notoryctids and caenolestids. A maximum parsimony algorithm favours ancestral ossified patella for the clade [Marsupialia + sparassodonts] and subsequent reductions into fibrocartilage in didelphids, dasyuromorphs and diprotodonts; but this result changed to agree more with the maximum likelihood results if the character state reconstructions were ordered. Thus, there is substantial homoplasy in marsupial patellae regardless of the evolutionary algorithm adopted. We contend that the most plausible inference, however, is that metatherians independently ossified their patellae at least three times in their evolution. Furthermore, the variability of the patellar state we observed, even within single species (e.g. M. rufogriseus), is fascinating and warrants further investigation, especially as it hints at developmental plasticity that might have been harnessed in marsupial evolution to drive the complex patterns inferred here.

Leptin Matures Aspects of Lung Structure and Function in the Ovine Fetus.

In human and ovine fetuses, glucocorticoids stimulate leptin secretion, although the extent to which leptin mediates the maturational effects of glucocorticoids on pulmonary development is unclear. This study investigated the effects of leptin administration on indices of lung structure and function before birth. Chronically catheterized singleton sheep fetuses were infused iv for 5 days with either saline or recombinant ovine leptin (0.5 mg/kg · d leptin (LEP), 0.5 LEP or 1.0 mg/kg · d, 1.0 LEP) from 125 days of gestation (term ∼145 d). Over the infusion, leptin administration increased plasma leptin, but not cortisol, concentrations. On the fifth day of infusion, 0.5 LEP reduced alveolar wall thickness and increased the volume at closing pressure of the pressure-volume deflation curve, interalveolar septal elastin content, secondary septal crest density, and the mRNA abundance of the leptin receptor (Ob-R) and surfactant protein (SP) B. Neither treatment influenced static lung compliance, maximal lung volume at 40 cmH2O, lung compartment volumes, alveolar surface area, pulmonary glycogen, protein content of the long form signaling Ob-Rb or phosphorylated signal transducers and activators of transcription-3, or mRNA levels of SP-A, C, or D, elastin, vascular endothelial growth factor-A, the vascular endothelial growth factor receptor 2, angiotensin-converting enzyme, peroxisome proliferator-activated receptor γ, or parathyroid hormone-related peptide. Leptin administration in the ovine fetus during late gestation promotes aspects of lung maturation, including up-regulation of SP-B.