Abstract: A total of 17 microsatellite deoxyribonucleic acid loci used routinely for horse parentage control were used to evaluate genetic diversity among normal Arabian horses and severe combined immunodeficiency (SCID) carrier Arabian horses (ArS) and normal Arab-Barb horses and SCID carrier Arab-Barb horses (ArbeS). On the basis of the genotype of 186 horses, mean allelic diversity was estimated as 6.82, 5.53, and 6.7059 in normal Arabian horses, ArS, and for both groups of Arab-Barb horses, respectively. Five specific alleles were observed in ArS and ArbeS, with one common with ArS at HMS6, whereas five alleles common between ArS and ArbeS had a high frequency. Expected and observed heterozygosity showed great heterogeneity in the population studied and were similar or higher when compared with other studies on Arabian horses. Coefficient of gene differentiation Gst of Nei associated with Nei's genetic distance and multivariate correspondence analysis indicated a possible differentiation between the studied populations when analyzed separately according to breed. Probability of assignment of a horse to a specific group was assessed using a full and partial Bayesian approach. In all, 80.6% of Arab horses and 78.2% of Arab-Barb horses were assigned properly with a partial Bayesian test, which provided better results than the full one. These findings will be useful for identification of SCID carrier horses by using the microsatellite deoxyribonucleic acid loci used routinely for horse parentage control in our laboratory.

Abstract: To date, a large amount of equine genetic data has been obtained regarding (i) extant domestic horses of various breeds from all over the world, (ii) ancient domestic horses, (iii) the extant Przewalski's wild horse, and (iv) the late Pleistocene wild horse from Eurasia and North America. Here, a review of mtDNA and Y chromosome marker analyses is presented in the context of horse domestication. High matrilineal (mtDNA) diversity, which can be found in both extant and ancient (domestic and wild) horses, has suggested that a high number of wild (and tamed) mares were domesticated. Alternatively, Y chromosome marker analysis revealed a single haplotype in all domestic horses analyzed; interestingly even a small population of extant Przewalski's wild horses showed two different Y chromosome haplotypes. It seems that an extreme male population bottleneck occurred due to domestication, while reduction in the female population was only moderate, leaving about 100 distinct haplotypes. For this reason, we speculate that domestication might have started when the appropriate stallion was found or was obtained by selection. Perhaps it had some unusual but special characteristics which could have accelerated the process of domestication. We doubt that only a single Y chromosome haplotype will be found in present-day domestic horses if there are no important differences between the founder stallion/s and the other stallions that were not included in the domestication. In the Eneolithic, tamed and wild mares have probably been spread all over Eurasia, although the number of animals was most likely very low and the populations were limited to a restricted area (e.g., taming centers). Only two subspecies of wild horses (Tarpan and Przewalski's wild horse) have survived up to recently. During the further process of domestication, mares (tamed or wild) were preferentially crossed to stallions having more desirable characteristics. We assume that mares from different regions varied in their morphology due to adaptation to their local environmental conditions. These data might explain rapid expansion of horse populations, as well as their rapid differentiation into various phenotypes during the early phase of domestication.

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.

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.