Abstract
In mammals, embryonic development are highly regulated morphogenetic processes that are tightly controlled by genetic elements. Failure of any one of these processes can result in embryonic malformation. The lysyl oxidase (LOX) family genes are closely related to human diseases. In this study, we investigated the essential role of lysyl oxidase-like 3 (LOXL3), a member of the LOX family, in embryonic development. Mice lacking LOXL3 exhibited perinatal lethality, and the deletion of the Loxl3 gene led to impaired development of the palate shelves, abnormalities in the cartilage primordia of the thoracic vertebrae and mild alveolar shrinkage. We found that the obvious decrease of collagen cross-links in palate and spine that was induced by the lack of LOXL3 resulted in cleft palate and spinal deformity. Thus, we provide critical in vivo evidence that LOXL3 is indispensable for mouse palatogenesis and vertebral column development. The Loxl3 gene may be a candidate disease gene resulting in cleft palate and spinal deformity.
Highlights
Lysyl oxidase (LOX) is an extracellular copper-dependent amine oxidase that has been traditionally believed to catalyse the covalent cross-linking of several fibrillar collagen types and the formation of desmosine and isodesmosine cross-links in elastin
We found that the obvious decrease of collagen cross-links in palate and spine that was induced by the lack of lysyl oxidase-like 3 (LOXL3) resulted in cleft palate and spinal deformity
The mouse Loxl3 gene was inactivated by a two-step method consisting of homologous recombination in ES cells followed by Cre-recombination in mice (Fig. 1A)
Summary
Lysyl oxidase (LOX) is an extracellular copper-dependent amine oxidase that has been traditionally believed to catalyse the covalent cross-linking of several fibrillar collagen types and the formation of desmosine and isodesmosine cross-links in elastin. Compared with LOX and LOXL1, there are four scavenger receptor cysteine-rich (SRCR) domains in the N-terminal region of LOXL2, LOXL3 and LOXL4 [1,2,3]. These SRCR domains, which are likely unrelated to catalytic activity, may confer novel distinct biological roles to these amine oxidases. LOXL3 and a variant LOXL3-sv have high amine oxidase activities in several collagen types and were suggested to have a possible functional role in bone development or maintenance [13].
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