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Author |
Cheung, C.; Akiyama, T.E.; Ward, J.M.; Nicol, C.J.; Feigenbaum, L.; Vinson, C.; Gonzalez, F.J. |
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Title |
Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha |
Type |
Journal Article |
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Year |
2004 |
Publication |
Cancer research |
Abbreviated Journal  |
Cancer Res |
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Volume |
64 |
Issue |
11 |
Pages |
3849-3854 |
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Keywords |
Animals; Anticholesteremic Agents/pharmacology; Carcinogens/pharmacology; Cell Division; DNA Replication/drug effects; Fatty Acids/metabolism; Hepatocytes/cytology/drug effects/metabolism/*physiology; Humans; Mice; Mice, Transgenic; Oxidation-Reduction; Peroxisome Proliferators/pharmacology; Pyrimidines/pharmacology; Receptors, Cytoplasmic and Nuclear/genetics/*physiology; Species Specificity; Transcription Factors/genetics/*physiology |
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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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Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA |
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0008-5472 |
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PMID:15172993 |
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no |
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Call Number |
refbase @ user @ |
Serial |
74 |
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Author |
Nicol, C.J.; Yoon, M.; Ward, J.M.; Yamashita, M.; Fukamachi, K.; Peters, J.M.; Gonzalez, F.J. |
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Title |
PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis |
Type |
Journal Article |
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Year |
2004 |
Publication |
Carcinogenesis |
Abbreviated Journal |
Carcinogenesis |
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Volume |
25 |
Issue |
9 |
Pages |
1747-1755 |
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Keywords |
9,10-Dimethyl-1,2-benzanthracene/*toxicity; Animals; DNA Primers/chemistry; Disease Susceptibility; Female; Heterozygote; Humans; Mammary Neoplasms, Experimental/chemically induced/*pathology; Mice; Ovarian Neoplasms/chemically induced/*pathology; RNA, Messenger/genetics/metabolism; Receptors, Cytoplasmic and Nuclear/genetics/*physiology; Reverse Transcriptase Polymerase Chain Reaction; Skin Neoplasms/chemically induced/*pathology; Survival Rate; Transcription Factors/genetics/*physiology; Zinc Fingers |
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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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Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA |
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ISSN |
0143-3334 |
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PMID:15073042 |
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no |
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Call Number |
refbase @ user @ |
Serial |
76 |
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Author |
Milinovich, G.J.; Trott, D.J.; Burrell, P.C.; van Eps, A.W.; Thoefner, M.B.; Blackall, L.L.; Al Jassim, R.A.M.; Morton, J.M.; Pollitt, C.C. |
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Title |
Changes in equine hindgut bacterial populations during oligofructose-induced laminitis |
Type |
Journal Article |
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Year |
2006 |
Publication |
Environmental Microbiology |
Abbreviated Journal |
Environ Microbiol |
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Volume |
8 |
Issue |
5 |
Pages |
885-898 |
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Keywords |
Animal Feed; Animals; Bacteria/classification/*isolation & purification; DNA, Bacterial/analysis; Disease Models, Animal; Feces/microbiology; Foot Diseases/etiology/microbiology/*veterinary; Horse Diseases/*etiology/metabolism/microbiology; Horses; In Situ Hybridization, Fluorescence; Intestines/*microbiology; Oligosaccharides/*administration & dosage/*metabolism; Phylogeny; Polymerase Chain Reaction; RNA, Bacterial/analysis; RNA, Ribosomal, 16S/analysis |
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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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Address |
Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Queensland, Australia. g.milinovich@uq.edu.au |
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English |
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Edition |
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ISSN |
1462-2912 |
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Notes |
PMID:16623745 |
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no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
2625 |
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Author |
Birch, H.L.; Bailey, A.J.; Goodship, A.E. |
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Title |
Macroscopic 'degeneration' of equine superficial digital flexor tendon is accompanied by a change in extracellular matrix composition |
Type |
Journal Article |
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Year |
1998 |
Publication |
Equine Veterinary Journal |
Abbreviated Journal |
Equine Vet J |
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Volume |
30 |
Issue |
6 |
Pages |
534-539 |
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Keywords |
Animals; Collagen/analysis; DNA/analysis; Extracellular Matrix/*chemistry; Glycosaminoglycans/analysis; Horses/injuries/*physiology; Immunohistochemistry; Rupture/veterinary; Tendon Injuries/metabolism/pathology/veterinary; Tendons/chemistry/*pathology; Water/analysis |
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Abstract |
Injuries to the superficial digital flexor tendon are common in horses required to gallop and jump at speed. Partial rupture of this tendon usually occurs in the central core of the midmetacarpal region and may be preceded by localised degenerative changes. Post mortem examination of apparently normal equine flexor tendons has revealed an abnormal macroscopic appearance in the central core, characterised by a reddish discolouration. We have previously shown that there is also physical damage to the collagen fibres. In the present study we tested the hypothesis that the abnormal appearance is accompanied by changes in the composition of the extracellular matrix of the tendon. Biochemical analysis of the extracellular matrix demonstrated an increase in total sulphated glycosaminoglycan content, increase in the proportion of type III collagen and decrease in collagen linked fluorescence in the central core of 'degenerated' tendons relative to tissue from the peripheral region of the same tendon. Dry matter content and total collagen content were not significantly different between tendon zones or normal and 'degenerated' tendons. These changes suggest a change in cell metabolism and matrix turnover in the central core of the tendon and are likely to contribute to a decrease in mechanical properties in this part of the tendon, predisposing to the characteristic partial rupture of the tendon. |
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Address |
Veterinary Basic Sciences, Royal Veterinary College, North Mymms, Hatfield, UK |
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English |
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ISSN |
0425-1644 |
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Notes |
PMID:9844973 |
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no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
3794 |
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Author |
Yokoyama, S.; Radlwimmer, F.B. |
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Title |
The molecular genetics of red and green color vision in mammals |
Type |
Journal Article |
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Year |
1999 |
Publication |
Genetics |
Abbreviated Journal |
Genetics |
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Volume |
153 |
Issue |
2 |
Pages |
919-932 |
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Keywords |
Amino Acid Sequence; Animals; Base Sequence; COS Cells; Cats; Color Perception/*genetics; DNA Primers; Deer; Dolphins; *Evolution, Molecular; Goats; Guinea Pigs; Horses; Humans; Mammals/*genetics/physiology; Mice; Molecular Sequence Data; Opsin/biosynthesis/chemistry/*genetics; *Phylogeny; Rabbits; Rats; Recombinant Proteins/biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; Sciuridae; Sequence Alignment; Sequence Homology, Amino Acid; Transfection |
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Abstract |
To elucidate the molecular mechanisms of red-green color vision in mammals, we have cloned and sequenced the red and green opsin cDNAs of cat (Felis catus), horse (Equus caballus), gray squirrel (Sciurus carolinensis), white-tailed deer (Odocoileus virginianus), and guinea pig (Cavia porcellus). These opsins were expressed in COS1 cells and reconstituted with 11-cis-retinal. The purified visual pigments of the cat, horse, squirrel, deer, and guinea pig have lambdamax values at 553, 545, 532, 531, and 516 nm, respectively, which are precise to within +/-1 nm. We also regenerated the “true” red pigment of goldfish (Carassius auratus), which has a lambdamax value at 559 +/- 4 nm. Multiple linear regression analyses show that S180A, H197Y, Y277F, T285A, and A308S shift the lambdamax values of the red and green pigments in mammals toward blue by 7, 28, 7, 15, and 16 nm, respectively, and the reverse amino acid changes toward red by the same extents. The additive effects of these amino acid changes fully explain the red-green color vision in a wide range of mammalian species, goldfish, American chameleon (Anolis carolinensis), and pigeon (Columba livia). |
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Address |
Department of Biology, Syracuse University, Syracuse, New York 13244, USA. syokoyam@mailbox.syr.edu |
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English |
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ISSN |
0016-6731 |
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Notes |
PMID:10511567 |
Approved |
no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
4063 |
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Author |
Zhao, C.J.; Qin, Y.H.; Lee, X.H.; Wu, C. |
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Title |
Molecular and cytogenetic paternity testing of a male offspring of a hinny |
Type |
Journal Article |
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Year |
2006 |
Publication |
Journal of Animal Breeding and Genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie |
Abbreviated Journal |
J Anim Breed Genet |
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Volume |
123 |
Issue |
6 |
Pages |
403-405 |
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Keywords |
Animals; Cytogenetic Analysis; DNA, Mitochondrial/genetics; Equidae/*genetics; Female; Horses/genetics; Hybridization, Genetic; Male; Microsatellite Repeats; Pedigree; Protamines/genetics; Sexual Behavior, Animal |
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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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Address |
Equine Center, China Agricultural University, Beijing, China |
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English |
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Abbreviated Series Title |
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ISSN |
0931-2668 |
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Notes |
PMID:17177697 |
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no |
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Call Number |
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Serial |
1846 |
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Author |
Ishida, N.; Oyunsuren, T.; Mashima, S.; Mukoyama, H.; Saitou, N. |
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Title |
Mitochondrial DNA sequences of various species of the genus Equus with special reference to the phylogenetic relationship between Przewalskii's wild horse and domestic horse |
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Journal Article |
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Year |
1995 |
Publication |
Journal of Molecular Evolution |
Abbreviated Journal |
J Mol Evol |
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Volume |
41 |
Issue |
2 |
Pages |
180-188 |
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Keywords |
Animals; Base Sequence; Chromosomes; Conserved Sequence/genetics; DNA, Mitochondrial/*genetics; Evolution; Genetic Variation/*genetics; Horses/*genetics; Molecular Sequence Data; *Phylogeny; RNA, Transfer, Pro/genetics; Sequence Alignment; Sequence Analysis, DNA |
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Abstract |
The noncoding region between tRNAPro and the large conserved sequence block is the most variable region in the mammalian mitochondrial DNA D-loop region. This variable region (ca. 270 bp) of four species of Equus, including Mongolian and Japanese native domestic horses as well as Przewalskii's (or Mongolian) wild horse, were sequenced. These data were compared with our recently published Thoroughbred horse mitochondrial DNA sequences. The evolutionary rate of this region among the four species of Equus was estimated to be 2-4 x 10(-8) per site per year. Phylogenetic trees of Equus species demonstrate that Przewalskii's wild horse is within the genetic variation among the domestic horse. This suggests that the chromosome number change (probably increase) of the Przewalskii's wild horse occurred rather recently. |
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Address |
Laboratory of Molecular and Cellular Biology, Japan Racing Association, Tokyo |
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English |
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0022-2844 |
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Notes |
PMID:7666447 |
Approved |
no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
5042 |
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Author |
Passler, S.; Pfeffer, M. |
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Title |
Detection of antibodies to alphaviruses and discrimination between antibodies to eastern and western equine encephalitis viruses in rabbit sera using a recombinant antigen and virus-specific monoclonal antibodies |
Type |
Journal Article |
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Year |
2003 |
Publication |
Journal of Veterinary Medicine. B, Infectious Diseases and Veterinary Public Health |
Abbreviated Journal |
J Vet Med B Infect Dis Vet Public Health |
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Volume |
50 |
Issue |
6 |
Pages |
265-269 |
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Keywords |
Animals; Antibodies, Monoclonal/*immunology; Antibodies, Viral/*analysis/blood; DNA Primers; Encephalitis Virus, Eastern Equine/genetics/*immunology; Encephalitis Virus, Western Equine/genetics/*immunology; Encephalomyelitis, Equine/*diagnosis/*virology; Epitopes; Fluorescent Antibody Technique/*veterinary; Horses; Rabbits; Recombination, Genetic; Reverse Transcriptase Polymerase Chain Reaction/veterinary |
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Abstract |
Three arthropod-borne alphaviruses, western equine encephalitis viruses (WEEV), eastern equine encephalitis viruses (EEEV) and Venezuelan equine encephalitis viruses are the aetiological agents of a sometimes severe encephalomyelitis in equines and humans in the New World. With regard to the different ecology and epidemiology of these viruses, a method applied in serological screening should be able to distinguish between them as well as other related members of the genus Alphavirus in the American continent. However, this has been hampered in the past by (a) the close antigenic relationship between alphaviruses in traditional serological assays, especially in the routinely used haemagglutination-inhibition, and (b) the need of biosafety level 3 facilities to grow the viral antigens. An epitope blocking assay using an EEEV glycoprotein E1-expressing recombinant Sindbis virus and virus-specific monoclonal antibodies (mAbs) binding to the E1 of EEEV (strain NJ/60) and the E1 of Sindbis virus was established using automated flow cytometry. The test was evaluated using sera of infected and vaccinated rabbits. A cut-off value of 30% inhibition for antigenic complex-specific seroconversion was found to be sufficient for the detection of the respective infection. By using three different mAbs in parallel, we were able to detect alphavirus genus-, EEEV- and WEEV-complex-specific serum antibodies. As this test is based on the inhibition of binding of virus-specific mAbs, sera of every origin other than mouse can be tested. Thus, this assay may prove useful in the serological screening of a variety of animal species during an outbreak investigation. |
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Address |
Institute for Medical Microbiology, Infectious and Epidemic Diseases, Veterinary Faculty, Ludwig-Maximilians-University, Munich, Germany |
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English |
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Abbreviated Series Title |
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Edition |
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ISSN |
0931-1793 |
ISBN |
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Notes |
PMID:14628996 |
Approved |
no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
2639 |
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Author |
Piro, M.; Benjouad, A.; Karom, A.; Nabich, A.; Benbihi, N.; El Allali, K.; Machmoum, M.; Ouragh, L. |
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Title |
Genetic Structure of Severe Combined Immunodeficiency Carrier Horses in Morocco Inferred by Microsatellite Data |
Type |
Journal Article |
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Year |
2011 |
Publication |
Journal of Equine Veterinary Science |
Abbreviated Journal |
J. Equine Vet. Sci. |
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Volume |
31 |
Issue |
11 |
Pages |
618-624 |
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Keywords |
Scid; Arab horses; Arab-Barb horses; Microsatellite; Dna; Genetic structure |
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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. |
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0737-0806 |
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no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
6657 |
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Author |
Traversa, D.; Giangaspero, A.; Galli, P.; Paoletti, B.; Otranto, D.; Gasser, R.B. |
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Title |
Specific identification of Habronema microstoma and Habronema muscae (Spirurida, Habronematidae) by PCR using markers in ribosomal DNA |
Type |
Journal Article |
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Year |
2004 |
Publication |
Molecular and Cellular Probes |
Abbreviated Journal |
Mol Cell Probes |
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Volume |
18 |
Issue |
4 |
Pages |
215-221 |
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Keywords |
Animals; Base Sequence; DNA, Ribosomal/blood/*genetics; Feces/parasitology; Genetic Markers; Horses/*parasitology; Molecular Sequence Data; Muscidae/*genetics; Polymerase Chain Reaction; Spirurida Infections/genetics; Spiruroidea/*genetics; Stomach/*parasitology |
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Abstract |
Gastric or cutaneous habronemosis caused by Habronema microstoma Creplin, 1849 and Habronema muscae Carter, 1865 is a parasitic disease of equids transmitted by muscid flies. There is a paucity of information on the epidemiology of this disease, which is mainly due to limitations with diagnosis in the live animal and with the identification of the parasites in the intermediate hosts. To overcome such limitations, a molecular approach, based on the use of genetic markers in the second internal transcribed spacer (ITS-2) of ribosomal DNA, was established for the two species of Habronema. Characterisation of the ITS-2 revealed sequence lengths and G+C contents of 296 bp and 29.5% for H. microstoma, and of 334 bp and 35.9% for H. muscae, respectively. Exploiting the sequence difference (approximately 40%) between the two species of nematode, primers were designed and tested by the polymerase chain reaction (PCR) for their specificity using a panel of control DNA samples from common equid endoparasites, and from host tissues, faeces or muscid flies. Effective amplification from each of the two species of Habronema was achieved from as little as 10 pg of genomic DNA. Hence, this molecular approach allows the specific identification and differentiation of the DNA from H. microstoma and H. muscae, and could thus provide a molecular tool for the specific detection of Habronema DNA (irrespective of developmental stage) from faeces, skin and muscid fly samples. The establishment of this tool has important implications for the specific diagnosis of clinical cases of gastric and cutaneous habronemosis in equids, and for studying the ecology and epidemiology of the two species of Habronema. |
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Address |
Department of Biomedical Comparative Sciences, Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy |
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Place of Publication |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Series Title |
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Series Volume |
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Edition |
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ISSN |
0890-8508 |
ISBN |
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Notes |
PMID:15271381 |
Approved |
no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
2634 |
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