Human LMO7 blocking peptide

The aim of our study was to investigate the potential association of mRNA expression and plasma levels of the LIM domain 7 (LMO7) gene with the pathogenesis of dilated cardiomyopathy (DCM). Two SNPs of the LMO7 gene were genotyped in 310 patients with DCM and 415 controls. Our results showed that SNP rs7986131 (p = 0.002, OR = 1.38, 95% CI = 1.12-1.71), but not SNP rs4884021, was associated with DCM in the Han Chinese population. Haplotype analysis showed that the haplotype GT was associated with increased DCM susceptibility while AC was a protective haplotype. The Cox multivariate survival analysis indicated that the rs7986131 TT genotype (HR 1.659, 95% CI = 1.122-2.454, p = 0.011) was an independent multivariate predictor for shorter overall survival in patients with DCM. LMO7 mRNA expression and plasma LMO7 levels were significantly decreased in DCM (p < 0.0001). Spearman correlation test revealed that the plasma LMO7 level was negatively associated with left ventricular end-diastolic diameter (r = -0.384, p = 0.01), left ventricular end-diastolic volume (r = -0.375, p = 0.012), and brain natriuretic peptide (r = -0.482, p = 0.001). Our study suggested that the LMO7 gene may play an important role in the pathogenesis of DCM in the Han Chinese population.

The Acrg minimal region is a 1.5-1.7 Mb domain defined by genetic complementation among deletions generated around Ednrb on chromosome 14 in mice. Mice homozygous for one of the deletions, Ednrb(s-1Acrg), exhibit embryonic lethality with defects associated with mesoderm development. We predicted that the region contains a single cluster of four genes that encode a TBC domain-containing protein (KIAA0603), a novel protein AK000009, the ubiquitin C-terminal hydrolase L3 (UCHL3) and an F-box/PDZ/LIM domain protein LMO7. A targeted internal deletion of Uchl3 (Uchl3(Delta3-7)) produced viable mice, eliminating this gene as a candidate for the embryonic lethality. To dissect the Acrg minimal region further, we utilized Cre-loxP-mediated chromosome engineering to generate a targeted 800 kb deletion (Lmo7(Delta800)) that removes the distal portion of the region. The deletion includes Uchl3, Lmo7 and an additional 500 kb downstream of the 3' end of Lmo7 where no genes are thought to reside. We found that similar to40% of mice homozygous for this deletion die between birth and weaning, and are severely runted. The remaining homozygotes are viable, thus ruling out Lmo7 as a single gene candidate for the Ednrb(s-1Acrg) embryonic lethality. Both Uchl3(Delta3-7) and Lmo7(Delta800) mutants displayed retinal degeneration, muscular degeneration and growth retardation, but the severity of the muscular degeneration and growth retardation were enhanced in Lmo7(Delta800) homozygotes. We suggest that the increase in severity may reflect an interaction between Uchl3 and Lmo7 in the ubiquitin-mediated protein degradation pathway.