Limb- and tendon-specific Adamtsl2 deletion identifies a role for ADAMTSL2 in tendon growth in a mouse model for geleophysic dysplasia.

Limb- and tendon-specific Adamtsl2 deletion identifies a role for ADAMTSL2 in tendon growth in a mouse model for geleophysic dysplasia. Matrix Biol. 2019 Feb 07;: Authors: Hubmacher D, Taye N, Balic Z, Thacker S, Adams SM, Birk DE, Schweitzer R, Apte SS Abstract Geleophysic dysplasia is a rare, frequently lethal condition characterized by severe short stature with progressive joint contractures, cardiac, pulmonary, and skin anomalies. Geleophysic dysplasia results from dominant fibrillin-1 (FBN1) or recessive ADAMTSL2 mutations, suggesting a functional link between ADAMTSL2 and fibrillin microfibrils. Mice lacking ADAMTSL2 die at birth, which has precluded analysis of postnatal limb development and mechanisms underlying the skeletal anomalies of geleophysic dysplasia. Here, detailed expression analysis of Adamtsl2 using an intragenic lacZ reporter shows strong Adamtsl2 expression in limb tendons. Expression in developing and growing bones is present in regions that are destined to become articular cartilage but is absent in growth plate cartilage. Consistent with strong tendon expression, Adamtsl2 conditional deletion in limb mesenchyme using Prx1-Cre led to tendon anomalies, albeit with normal collagen fibrils, and distal limb shortening, providing a mouse model for geleophysic dysplasia. Unexpectedly, conditional Adamtsl2 deletion using Scx-Cre, a tendon-specific Cre-deleter strain, which does not delete in cartilage, also impaired...
Source: Matrix Biology - Category: Molecular Biology Authors: Tags: Matrix Biol Source Type: research