Elsevier

Matrix Biology

Volume 19, Issue 2, 1 May 2000, Pages 179-183
Matrix Biology

Short Note
The mouse lysyl oxidase-like 2 gene (mLOXL2) maps to chromosome 14 and is highly expressed in skin, lung and thymus

https://doi.org/10.1016/S0945-053X(00)00061-5Get rights and content

Abstract

The predicted amino acid sequence derived from a mouse expressed sequence tag (EST) contig contained two domains that are highly conserved among members of the lysyl oxidase gene family: a copper binding-site with four histidines and a catalytic domain that includes a tryptophan residue. This new cDNA sequence showed the highest level of sequence homology with the human loxl2 cDNA and suggested that it encoded the mouse equivalent of hLOXL2. The mLOXL2 gene was mapped to chromosome 14 by radiation hybrid analysis. The mLOXL2 locus was tightly linked with a LOD score over 9 to the marker D14Mit32. The mLOXL2 gene is expressed as a 4-kb mRNA in almost all tissues analyzed, with highest levels of mRNA in skin, lung and thymus.

Introduction

Over the last two decades, studies on lysyl oxidase (LOX) have been principally focused on the biochemical characteristics and cross-linking activities of this amine oxidase toward collagen and elastin substrates. More recently, several new biological functions have been attributed to lysyl oxidase, ranging from developmental regulation (Butler et al., 1987) to tumor suppression and cell growth control (Di Donato et al., 1997). Reports of several human and mouse lysyl oxidase-like genes and cDNAs indicate that lysyl oxidase is a family of proteins that may be responsible for these diverse functions. Until now, four human genes, lysyl oxidase (LOX, Hamalainen et al., 1993), lysyl oxidase-like (LOXL, Kim et al., 1995), lysyl oxidase-like 2 (LOXL2, Jourdan-Le Saux et al., 1999) and a novel lysyl oxidase-related cDNA (Lor, Saito et al., 1997) have been described. Two of the corresponding mouse genes, mLOX and mLOXL, and a new mouse cDNA, lysyl oxidase-related 2 or Lor-2, have also been reported (Chang et al., 1993, Jang et al., 1999, Kim et al., 1999). These genes have been mapped to chromosomes 18, 9 and 6, respectively.

Two highly conserved domains characterize this family of enzymes: a copper-binding site containing four histidines and a catalytic domain with a tyrosine (Y) residue that participates, together with a lysine residue, in the formation of a carbonyl cofactor. The sequence similarities between LOX and the LOXL cDNAs, specifically within the copper binding site and the active site, suggest that these proteins may have related functions. In an induced mouse liver fibrosis model, LOXL gene expression was clearly associated with early changes in liver fibrosis, particularly with an increase in the appearance of the mRNA encoding type III collagen, while steady state levels of LOX mRNA paralleled changes in type I collagen mRNA levels (Kim et al., 1999). These results suggest that lysine-derived cross-links in type III collagen might be catalyzed by LOXL. No specific functions have been assigned to the lysyl oxidase related-2 protein, although the Lor-2 gene was reported as a potential candidate gene for mnd2, an autosomal recessive disorder characterized by muscle dystrophy and wasting (Jones et al., 1993).

In this manuscript we report the cDNA sequence, the chromosomal localization and tissue expression of the fourth member of the mouse LOX family, the lysyl oxidase-like 2 (mLOXL2) gene.

Section snippets

The mouse LOXL2 cDNA sequence

In an attempt to identify new members of the emerging lysyl oxidase gene family, a Blast search using the human LOXL2 cDNA sequence, identified four mouse cDNA sequences in the GenBank database with 85–89% homology to hLOXL2. A cDNA sequence of 905 bp was generated from these overlapping expressed sequence tag (EST) clones (IMAGE Consortium clones 820685, 820637, 586150 and 820612). The sequence comparison of this cDNA sequence (GenBank access number AF117951) with the hLOXL2 cDNA (Jourdan-Le

LOXL2 ESTs and sequence analysis

The human loxl2 cDNA sequence (GenBank access number AF117949) was used to search the mouse EST database by the Blast search program (http://www.ncbi.nlm.nih.gov/cgi-bin/BLAST). DNA sequencing of ESTs found to have significant homology to the human loxl2 cDNA, were performed using the Thermo Sequenase-radiolabeled terminator cycle sequencing kit (Amersham Life Science Inc., Arlington Heights, IL) as described by the manufacturer.

Radiation hybrid mapping

The 100 clones of the T31 Mouse Radiation Hybrid panel (Research

Acknowledgements

This work was supported by NIH grants CA766580 and RR03061.

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