Disease relevance of Loxl1

• Recently, it was reported that mice with null mutations in lysyl oxidase-like 1 (LOXL1) develop pelvic organ prolapse [1].
• These results revealed the coincident appearance of increased steady state levels of LOXL mRNA and type III procollagen mRNA early in the development of liver fibrosis [2].
• Lysyl oxidase-like protein localizes to sites of de novo fibrinogenesis in fibrosis and in the early stromal reaction of ductal breast carcinomas [3].

High impact information on Loxl1

• Thus elastin polymer deposition is a crucial aspect of elastic fiber maintenance and is dependent on LOXL1, which serves both as a cross-linking enzyme and an element of the scaffold to ensure spatially defined deposition of elastin [4].
• Deposition of fibulin-5 on microfibrils promotes coacervation and alignment of tropoelastins on microfibrils, and also facilitates cross-linking of tropoelastin by tethering lysyl oxidase-like 1, 2, and 4 enzymes [5].
• The temporal relationship between LOX mRNA and protein, processing of LOXL1 protein, FBLN5 and tropoelastin protein, and desmosine content in the vagina suggest that a burst of elastic fiber assembly and cross linking occurs in the vaginal wall postpartum [1].
• LOXL1 deficiency caused an inability of reproductive tissues to replenish elastic fibers after parturition, leading to pelvic organ prolapse, weakening of the vaginal wall, paraurethral pathology, and lower urinary tract dysfunction [6].
• However, the LOXL catalytic domain without the pro-region was secreted into the medium but did not associate with matrix [7].

Biological context of Loxl1

• The rc locus was mapped at 32.0 cM on chromosome 9, close to the loxl gene [8].
• LOXL is expressed at high levels in the skin and heart, where the rc mice show strong phenotype [8].
• Oligonucleotides complementary to conserved domains within exons 4 and 5 of the human lysyl oxidase-like gene were used to amplify the corresponding segment from mouse genomic DNA [9].
• An AluI restriction site polymorphism within intron 4 was used to map the mouse lysyl oxidase-like gene (Loxl) to mouse Chromosome 9 in a region that shares linkage conservation with human chromosome 15q24, to which the LOXL was recently mapped [9].

Anatomical context of Loxl1

• In rc mice, the loxl mRNA was reduced in the skin and the LOXL protein in the heart, dermis, atrophic hair follicles, and sebaceous glands [8].
• Thus, contrary to expectation, structural changes in the hippocampus of LOXL -/- mice did not affect synaptic remodeling in a manner that impaired the establishment of LTP [10].
• Electrical recordings were obtained in 300-mum hippocampal slices in dentate and CA1 pyramidal cell layers in age-matched wild type and LOXL null mice [10].
• Central nervous system, uterus, heart, and leukocyte expression of the LOXL3 gene, encoding a novel lysyl oxidase-like protein [11].

Associations of Loxl1 with chemical compounds

• These findings suggest that the LOXL protein (possibly an isoform of lysyl oxidase) is involved in the development of lysine-derived cross-links in collagenous substrates [2].

Other interactions of Loxl1

• The expression pattern and the genetic proximity to rc suggested loxl as a potential candidate gene [8].
• Lysyl oxidase-like (LOXL) protein is a novel copper-containing amine oxidase that is required for the cross-linking of elastin and collagen in vitro [8].

References