Isolation, characterization and genetic analysis of canine GATA4 gene in a family of Doberman Pinschers with an atrial septal defect.

GATA4 is expressed early in the developing heart where it plays a key role in regulating the expression of genes encoding myocardial contractile proteins. Gene mutations in the human GATA4 have been implicated in various congenital heart defects (CHD), including atrial septal defect (ASD). Although ASD is the third most common CHD in humans, it is generally rare in dogs and cats.

Myoblasts isolated from hypertrophy-responsive callipyge muscles show altered growth rates and increased resistance to serum deprivation-induced apoptosis.

Back and hind limb muscles of sheep paternally heterozygous for the callipyge single nucleotide polymorphism undergo extensive hypertrophy shortly after birth. We have established cell cultures from foetal semitendinosus and longissimus dorsi muscles of normal and callipyge animals. Cultures were assessed for rates of proliferation, cell death, myogenicity and DLK1 expression.

Genetic screening of the canine connexin 40 gene in dogs with inherited cardiac conduction defects.

Connexin 40 (Cx40) is a gap-junction protein expressed in the heart where it mediates the coordinated electrical activation of the atria and ventricular conduction tissues, facilitates cell-to-cell adhesion, and provides pathways for direct intercellular communication. Recent studies have shown that Cx40 null mice have cardiac conduction abnormalities with a very high incidence of cardiac malformations in heterozygous (18%) and homozygous (33%) animals, indicating that Cx40 plays a vital role in cardiomorphogenesis. Since several inherited cardiac conduction defects have also been found in dogs, we hypothesized that the clinical findings are genetically linked to a tissue-specific mutation or mutations in the canine Cx40 gene.

Congenital heart diseases in small animals: part I. Genetic pathways and potential candidate genes.

Proper cardiac morphogenesis requires a series of specific cell and tissue interactions driven by several cardiac transcription factors and downstream cardiac genes. To date, a number of genetic aetiologies responsible for human congenital heart defects (CHDs) have been identified, although none has been found for CHDs in small animals. Most gene mutations responsible for human CHDs exist in genetic pathways associated with cardiomorphogenesis.

Muscle costameric protein, Chisel/Smpx, associates with focal adhesion complexes and modulates cell spreading in vitro via a Rac1/p38 pathway.

The murine X-linked gene Chisel (Csl/Smpx) encodes a 9-kDa protein that associates in heart and skeletal muscle cells with the costameric cytoskeleton, implicated in maintaining muscle integrity and responses to biomechanical stress. After expression in C2C12 myoblasts, MYC epitope-tagged Csl co-localized with actin networks at peripheral membranes, and with focal adhesion proteins vinculin, paxillin, integrin beta1, and the small GTPase Rac1. Csl could be co-immunoprecipitated with vinculin from extracts of C2C12 cells and native muscle.

Evaluation of haplotypes associated with copper toxicosis in Bedlington Terriers in Australia.

Objective: To evaluate the haplotype distribution associated with the copper toxicosis gene and the segregation of the mutated allele in a Bedlington Terrier population in Australia.

Animals: 131 Bedlington Terriers.

Procedure: Samples of DNA and RNA were obtained from each dog.

Functional consequences of the G235R mutation in liver arginase leading to hyperargininemia.

Hyperargininemia is a rare autosomal disorder that results from a deficiency in hepatic type I arginase. This deficiency is the consequence of random point mutations that occur throughout the gene. The G235R patient mutation has been proposed to affect the catalytic activity and structural integrity of the protein [D.