Investigation of the effect of exercise on the innate immunity in horses

Poster (2012, October 19)

Increased hypoxia-inducible factor 1alpha expression in lung cells of horses with recurrent airway obstruction.

in BMC Veterinary Research (2012), 8(1), 64

ABSTRACT: BACKGROUND: Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological ... [more ▼]

ABSTRACT: BACKGROUND: Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological processes responsible for the development and the persistence of airway inflammation are still largely unknown. Hypoxia-inducible factor (Hif) is mainly known as a major regulator of energy homeostasis and cellular adaptation to hypoxia. More recently however, Hif also emerged as an essential regulator of innate immune responses. Here, we aimed at investigating the potential involvement of Hif1-alpha in myeloid cells in horse with recurrent airway obstruction. RESULTS: In vitro, we observed that Hif is expressed in equine myeloid cells after hay dust stimulation and regulates genes such as tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGF-A). We further showed in vivo that airway challenge with hay dust upregulated Hif1-alpha mRNA expression in myeloid cells from the bronchoalveolar lavage fluid (BALF) of healthy and RAO-affected horses, with a more pronounced effect in cells from RAO-affected horses. Finally, Hif1-alpha mRNA expression in BALF cells from challenged horses correlated positively with lung dysfunction. CONCLUSION: Taken together, our results suggest an important role for Hif1-alpha in myeloid cells during hay dust-induced inflammation in horses with RAO. We therefore propose that future research aiming at functional inactivation of Hif1 in lung myeloid cells could open new therapeutic perspectives for RAO. [less ▲]

Investigation of the innate immunity in the lower respiratory tract in exercising horses

in Proceedings of the 1st Scientific Meeting of the Faculty of Veterinary Medicine (2011)

Polymorphic miRNA-target interactions : A Novel Source of Phenotypic Variation

in Cold Spring Harbor Symposia on Quantitative Biology (2006, June), 71

Studying the muscular hypertrophy of Texel sheep by forward genetics, we have identified an A-to-G transition in the 3'UTRof the GDF8 gene that reveals an illegitimate target site for microRNAs miR-1 and ... [more ▼]

Studying the muscular hypertrophy of Texel sheep by forward genetics, we have identified an A-to-G transition in the 3'UTRof the GDF8 gene that reveals an illegitimate target site for microRNAs miR-1 and miR-206 that are highly expressed in skeletal muscle. This causes the down-regulation of this muscle-specific chalone and hence contributes to the muscular hypertrophyof Texel sheep. We demonstrate that polymorphisms which alter the content of putative miRNA target sites are commonin human and mice, and provide evidence that both conserved and nonconserved target sites are selectively constrained. Wespeculate that these polymorphisms might be important mediators of phenotypic variation including disease. To facilitatestudies along those lines, we have constructed a database (www.patrocles.org) listing putative polymorphic microRNA–targetinteractions. [less ▲]

A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep.

in Nature Genetics (2006), 38(7), 813-8

Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov x Texel F2 population. We ... [more ▼]

Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov x Texel F2 population. We mapped a quantitative trait locus with a major effect on muscle mass to chromosome 2 and subsequently fine-mapped it to a chromosome interval encompassing the myostatin (GDF8) gene. We herein demonstrate that the GDF8 allele of Texel sheep is characterized by a G to A transition in the 3' UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs) that are highly expressed in skeletal muscle. This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep. Analysis of SNP databases for humans and mice demonstrates that mutations creating or destroying putative miRNA target sites are abundant and might be important effectors of phenotypic variation. [less ▲]

Positional cloning and genetic engineering of the myostatin gene causing double muscling in cattle

in Annales de Médecine Vétérinaire (2005), 149(3), 135-147

Double-muscling in cattle is a generalised hypertrophy of skeletal muscle resulting from a hyperplasia of the myofibers. Using a positional cloning strategy, we have identified the gene underlying double ... [more ▼]

Double-muscling in cattle is a generalised hypertrophy of skeletal muscle resulting from a hyperplasia of the myofibers. Using a positional cloning strategy, we have identified the gene underlying double-muscling, namely myostatin, and causal loss-of-function mutations therein. Myostatin is a novel member of the TGF-beta superfamily of growth and differentiation factors. Using conditional gene targeting in a murine model, we have demonstrated that post-natal muscle specific inactivation of the myostatin gene causes full-blown double muscling. This demonstrates the potential value of myostatin antagonist whether to promote muscle regeneration in patients suffering from muscle wasting disease, or to enhance meat production in livestock species. Finally, by targeting a myostatin transinhibitor on the Y chromosome, we have demonstrated in the mouse the feasibility of a more efficient cattle production system combining superior beef production abilities for bulls and dairy abilities for cows. [less ▲]

Modulating skeletal muscle mass by postnatal, muscle-specific inactivation of the myostatin gene.

in Genesis (New York, N.Y. : 2000) (2003), 35(4), 227-38

By using a conditional gene targeting approach exploiting the cre-lox system, we show that postnatal inactivation of the myostatin gene in striated muscle is sufficient to cause a generalized muscular ... [more ▼]

By using a conditional gene targeting approach exploiting the cre-lox system, we show that postnatal inactivation of the myostatin gene in striated muscle is sufficient to cause a generalized muscular hypertrophy of the same magnitude as that observed for constitutive myostatin knockout mice. This formally demonstrates that striated muscle is the production site of functional myostatin and that this member of the TGFbeta family of growth and differentiation factors regulates muscle mass not only during early embryogenesis but throughout development. It indicates that myostatin antagonist could be used to treat muscle wasting and to promote muscle growth in man and animals. [less ▲]

High-Resolution, Human-Bovine Comparative Mapping Based on a Closed Yac Contig Spanning the Bovine Mh Locus

in Mammalian Genome : Official Journal of the International Mammalian Genome Society (1999), 10(3), 289-93

A closed YAC contig spanning the mh locus was assembled by STS content mapping with seven microsatellite markers, eight genes or EST, and nine STS corresponding to YAC ends. The contig comprises 27 YACs ... [more ▼]

A closed YAC contig spanning the mh locus was assembled by STS content mapping with seven microsatellite markers, eight genes or EST, and nine STS corresponding to YAC ends. The contig comprises 27 YACs, has an average depth of 4.3 YACs, and spans an estimated 1.2 Mb. A linkage map was constructed based on five of the microsatellite markers anchored to the contig and shown to span 7 cM, yielding a ratio of 160 kb/1 cM for the corresponding chromosome region. Comparative mapping data indicate that the constructed contig spans an evolutionary breakpoint connecting two chromosome segments that are syntenic but not adjacent in the human. Consolidation of human gene order by means of whole genome radiation hybrids and its comparison with the bovine order as inferred from the contig confirm conservation of gene order within segments. [less ▲]

A Deletion in the Bovine Myostatin Gene Causes the Double-Muscled Phenotype in Cattle

in Nature Genetics (1997), 17(1), 71-74

An exceptional muscle development commonly referred to as 'double-muscled' (Fig. 1) has been seen in several cattle breeds and has attracted considerable attention from beef producers. Double-muscled ... [more ▼]

An exceptional muscle development commonly referred to as 'double-muscled' (Fig. 1) has been seen in several cattle breeds and has attracted considerable attention from beef producers. Double-muscled animals are characterized by an increase in muscle mass of about 20%, due to general skeletal-muscle hyperplasia-that is, an increase in the number of muscle fibers rather than in their individual diameter. Although the hereditary nature of the double-muscled condition was recognized early on, the precise mode of inheritance has remained controversial; monogenic (domainant and recessive), oligogenic and polygenic models have been proposed. In the Belgian Blue cattle breed (BBCB), segregation analysis performed both in experimental crosses and in the outbred population suggested an autosomal recessive inheritance. This was confirmed when the muscular hypertrophy (mh) locus was mapped 3.1 cM from microsatellite TGLA44 on the centromeric end of bovine chromosome 2 (ref. 5). We used a positional candidate approach to demonstrate that a mutation in bovine MSTN, which encodes myostatin, a member of the TGF beta superfamily, is responsible for the double-muscled phenotype. We report an 11-bp deletion in the coding sequence for the bioactive carboxy-terminal domain of the protein causing the muscular hypertrophy observed in Belgian Blue cattle. [less ▲]