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Cheung, C., Akiyama, T. E., Ward, J. M., Nicol, C. J., Feigenbaum, L., Vinson, C., et al. (2004). Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha. Cancer Res, 64(11), 3849–3854.
Abstract: Lipid-lowering fibrate drugs function as agonists for the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). Sustained activation of PPARalpha leads to the development of liver tumors in rats and mice. However, humans appear to be resistant to the induction of peroxisome proliferation and the development of liver cancer by fibrate drugs. The molecular basis of this species difference is not known. To examine the mechanism determining species differences in peroxisome proliferator response between mice and humans, a PPARalpha-humanized mouse line was generated in which the human PPARalpha was expressed in liver under control of the tetracycline responsive regulatory system. The PPARalpha-humanized and wild-type mice responded to treatment with the potent PPARalpha ligand Wy-14643 as revealed by induction of genes encoding peroxisomal and mitochondrial fatty acid metabolizing enzymes and resultant decrease of serum triglycerides. However, surprisingly, only the wild-type mice and not the PPARalpha-humanized mice exhibited hepatocellular proliferation as revealed by elevation of cell cycle control genes, increased incorporation of 5-bromo-2'-deoxyuridine into hepatocyte nuclei, and hepatomegaly. These studies establish that following ligand activation, the PPARalpha-mediated pathways controlling lipid metabolism are independent from those controlling the cell proliferation pathways. These findings also suggest that structural differences between human and mouse PPARalpha are responsible for the differential susceptibility to the development of hepatocarcinomas observed after treatment with fibrates. The PPARalpha-humanized mice should serve as models for use in drug development and human risk assessment and to determine the mechanism of hepatocarcinogenesis of peroxisome proliferators.
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Nicol, C. J., Yoon, M., Ward, J. M., Yamashita, M., Fukamachi, K., Peters, J. M., et al. (2004). PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis. Carcinogenesis, 25(9), 1747–1755.
Abstract: Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, plays a role in adipocyte differentiation, type II diabetes, macrophage response to inflammation and is suggested to influence carcinogen-induced colon cancer. Studies done in vitro and in vivo also revealed that PPARgamma ligands might promote differentiation and/or regression of mammary tumors. To directly evaluate the role of PPARgamma in mammary carcinogenesis, PPARgamma wild-type (+/+) or heterozygous (+/-) mice were administered 1 mg 7,12-dimethylbenz[a]anthracene (DMBA) by gavage once a week for 6 weeks and followed for a total of 25 weeks. Compared with congenic PPARgamma(+/+) littermate controls, PPARgamma(+/-) mice had early evidence for increased susceptibility to DMBA-mediated carcinogenesis based on a 1.6-fold increase in the percentage of mice with skin papillomas, as well as a 1.7-fold increase in the numbers of skin papillomas per mouse (P < 0.05). Similarly, PPARgamma(+/-) mice also had a 1.5-fold decreased survival rate (P = 0.059), and a 1.7-fold increased incidence of total tumors per mouse (P < 0.01). Moreover, PPARgamma(+/-) mice had an almost 3-fold increase in mammary adenocarcinomas (P < 0.05), an over 3-fold increase in ovarian granulosa cell carcinomas (P < 0.05), an over 3-fold increase in malignant tumors (P < 0.02) and a 4.6-fold increase in metastatic incidence. These results are the first to demonstrate an increased susceptibility in vivo of PPARgamma haploinsufficiency to DMBA-mediated carcinogenesis and suggest that PPARgamma may act as a tumor modifier of skin, ovarian and breast cancers. The data also support evidence suggesting a beneficial role for PPARgamma-specific ligands in the chemoprevention of mammary, ovarian and skin carcinogenesis.
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Jansen, T., Forster, P., Levine, M. A., Oelke, H., Hurles, M., Renfrew, C., et al. (2002). Mitochondrial DNA and the origins of the domestic horse. Proc. Natl. Acad. Sci. U.S.A., 99(16), 10905–10910.
Abstract: The place and date of the domestication of the horse has long been a matter for debate among archaeologists. To determine whether horses were domesticated from one or several ancestral horse populations, we sequenced the mitochondrial D-loop for 318 horses from 25 oriental and European breeds, including American mustangs. Adding these sequences to previously published data, the total comes to 652, the largest currently available database. From these sequences, a phylogenetic network was constructed that showed that most of the 93 different mitochondrial (mt)DNA types grouped into 17 distinct phylogenetic clusters. Several of the clusters correspond to breeds and/or geographic areas, notably cluster A2, which is specific to Przewalski's horses, cluster C1, which is distinctive for northern European ponies, and cluster D1, which is well represented in Iberian and northwest African breeds. A consideration of the horse mtDNA mutation rate together with the archaeological timeframe for domestication requires at least 77 successfully breeding mares recruited from the wild. The extensive genetic diversity of these 77 ancestral mares leads us to conclude that several distinct horse populations were involved in the domestication of the horse.
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Zhao, C. J., Qin, Y. H., Lee, X. H., & Wu, C. (2006). Molecular and cytogenetic paternity testing of a male offspring of a hinny. J Anim Breed Genet, 123(6), 403–405.
Abstract: An alleged male foal of a female mule, whose sire and grandparents were unknown, was identified for its pedigree. Parentage testing was conducted by comparing polymorphism of 12 microsatellite DNA sites and mitochondrial D-loop sequences of the male foal and the female mule. Both the sequence analysis of species-specific DNA fragments and a cytogenetic analysis were performed to identify the species of the foal and its parents. The results showed that the alleged female mule is actually a hinny, and the male foal, which possesses 62 chromosomes, qualifies as an offspring of the female hinny and a jack donkey.
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Macfadden, B. J. (2005). Evolution. Fossil horses--evidence for evolution. Science, 307(5716), 1728–1730.
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Ishida, N., Hirano, T., & Mukoyama, H. (1994). Detection of aberrant alleles in the D-loop region of equine mitochondrial DNA by single-strand conformation polymorphism (SSCP) analysis. Anim Genet, 25(4), 287.
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Breen, M., Downs, P., Irvin, Z., & Bell, K. (1994). Intrageneric amplification of horse microsatellite markers with emphasis on the Przewalski's horse (E. przewalskii). Anim Genet, 25(6), 401–405.
Abstract: Primer sequences flanking 13 microsatellite loci isolated from the domestic horse (E. caballus) were successfully used to amplify homologous loci in the Przewalski's horse (E. przewalskii). The results demonstrate that the level of polymorphism at all 13 loci in the Przewalski's horse was comparable to that in the domestic horse and the overall exclusion probability in the Przewalski's horse was calculated to be 0.9994. The results suggest that it should be possible to use E. caballus-derived microsatellite markers to provide parentage verification and additional valuable information to the captive management of E. przewalskii. The ability to amplify corresponding loci in the remaining five species of the genus was also confirmed, illustrating the general application of markers isolated from the domestic horse to the evaluation of polymorphism in the other six species of the genus.
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Burke, D., Cieplucha, C., Cass, J., Russell, F., & Fry, G. (2002). Win-shift and win-stay learning in the short-beaked echidna (Tachyglossus aculeatus). Anim. Cogn., 5(2), 79–84.
Abstract: Numerous previous investigators have explained species differences in spatial memory performance in terms of differences in foraging ecology. In three experiments we attempted to extend these findings by examining the extent to which the spatial memory performance of echidnas (or “spiny anteaters”) can be understood in terms of the spatio-temporal distribution of their prey (ants and termites). This is a species and a foraging situation that have not been examined in this way before. Echidnas were better able to learn to avoid a previously rewarding location (to “win-shift”) than to learn to return to a previously rewarding location (to “win-stay”), at short retention intervals, but were unable to learn either of these strategies at retention intervals of 90 min. The short retention interval results support the ecological hypothesis, but the long retention interval results do not.
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Muscatello, G., Anderson, G. A., Gilkerson, J. R., & Browning, G. F. (2006). Associations between the ecology of virulent Rhodococcus equi and the epidemiology of R. equi pneumonia on Australian thoroughbred farms. Appl Environ Microbiol, 72(9), 6152–6160.
Abstract: The ecology of virulent strains of Rhodococcus equi on horse farms is likely to influence the prevalence and severity of R. equi pneumonia in foals. This study examined the association between the ecology of virulent R. equi and the epidemiology of R. equi pneumonia by collecting air and soil samples over two breeding seasons (28 farm-year combinations) on Thoroughbred breeding farms with different reported prevalences of R. equi pneumonia. Colony blotting and DNA hybridization were used to detect and measure concentrations of virulent R. equi. The prevalence of R. equi pneumonia was associated with the airborne burden of virulent R. equi (both the concentration and the proportion of R. equi bacteria that were virulent) but was not associated with the burden of virulent R. equi in the soil. Univariable screening and multivariable model building were used to evaluate the effect of environmental and management factors on virulent R. equi burdens. Lower soil moisture concentrations and lower pasture heights were significantly associated with elevated airborne concentrations of virulent R. equi, as were the holding pens and lanes, which typically were sandy, dry, and devoid of pasture cover. Few variables appeared to influence concentrations of virulent R. equi in soil. Acidic soil conditions may have contributed to an elevated proportion of virulent strains within the R. equi population. Environmental management strategies that aim to reduce the level of exposure of susceptible foals to airborne virulent R. equi are most likely to reduce the impact of R. equi pneumonia on endemically affected farms.
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Milinovich, G. J., Trott, D. J., Burrell, P. C., van Eps, A. W., Thoefner, M. B., Blackall, L. L., et al. (2006). Changes in equine hindgut bacterial populations during oligofructose-induced laminitis. Environ Microbiol, 8(5), 885–898.
Abstract: In the horse, carbohydrate overload is thought to play an integral role in the onset of laminitis by drastically altering the profile of bacterial populations in the hindgut. The objectives of this study were to develop and validate microbial ecology methods to monitor changes in bacterial populations throughout the course of experimentally induced laminitis and to identify the predominant oligofructose-utilizing organisms. Laminitis was induced in five horses by administration of oligofructose. Faecal specimens were collected at 8 h intervals from 72 h before to 72 h after the administration of oligofructose. Hindgut microbiota able to utilize oligofructose were enumerated throughout the course of the experiment using habitat-simulating medium. Isolates were collected and representatives identified by 16S rRNA gene sequencing. The majority of these isolates collected belonged to the genus Streptococcus, 91% of which were identified as being most closely related to Streptococcus infantarius ssp. coli. Furthermore, S. infantarius ssp. coli was the predominant oligofructose-utilizing organism isolated before the onset of lameness. Fluorescence in situ hybridization probes developed to specifically target the isolated Streptococcus spp. demonstrated marked population increases between 8 and 16 h post oligofructose administration. This was followed by a rapid population decline which corresponded with a sharp decline in faecal pH and subsequently lameness at 24-32 h post oligofructose administration. This research suggests that streptococci within the Streptococcus bovis/equinus complex may be involved in the series of events which precede the onset of laminitis in the horse.
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