Assessment of Lipopolysaccharide, Isoproterenol and Phenylephrine Induced Pathophysiology in Lipoic Acid Synthase Deficient Mice

α-Lipoic acid is a potent antioxidant, and also an essential cofactor for PDH and α-KDH complexes in mitochondria. Investigations have shown complex human diseases are associated with oxidative stress. As preventative and therapeutic purposes, studies have evaluated effects of lipoic acid on complex human diseases, however, its molecular mechanisms and effects remained unknown. In this study, we examined the effects of heterozygous Lias deficiency on LPS induced inflammation and adrenergic agonist induced cardiac hypertrophy. We observed increased sensitivity of Lias heterozygous mice with elevation of TNF-α, decreased and delayed recovery of leukocyte and platelet counts accompanied with liver necrosis lung inflammation on LPS stimuli. Upon adrenergic agonist stimulation, both genotypes developed hypertrophy with increased HW/BW ratio and fibrosis in the heart, however, we observed protective effect of Lias deficiency upon stimulation. Our data indicates that Lias deficiency results in increased sensitivity upon LPS stimulation, however, protective effect against cardiac stimulation

Genetic reduction of lipoic acid synthase expression modestly increases atherosclerosis in male, but not in female, apolipoprotein E-deficient mice

To evaluate the effects of a genetic reduction of Lias gene expression on atherosclerosis development

The Paternal Gene of the DDK Syndrome Maps to the Schlafen Gene Cluster on Mouse Chromosome 11

The DDK syndrome is an early embryonic lethal phenotype observed in crosses between females of the DDK inbred mouse strain and many non-DDK males. Lethality results from an incompatibility between a maternal DDK factor and a non-DDK paternal gene, both of which have been mapped to the Ovum mutant (Om) locus on mouse chromosome 11. Here we define a 465-kb candidate interval for the paternal gene by recombinant progeny testing. To further refine the candidate interval we determined whether males from 17 classical and wild-derived inbred strains are interfertile with DDK females. We conclude that the incompatible paternal allele arose in the Mus musculus domesticus lineage and that incompatible strains should share a common haplotype spanning the paternal gene. We tested for association between paternal allele compatibility/incompatibility and 167 genetic variants located in the candidate interval. Two diallelic SNPs, located in the Schlafen gene cluster, are completely predictive of the polar-lethal phenotype. These SNPs also predict the compatible or incompatible status of males of five additional strains