A new Adamts9 conditional mouse allele identifies its non‐redundant role in interdigital web regression. Issue 7 (8th May 2014)

• Record Type: Journal Article
• Authors: Dubail, Johanne; Aramaki‐Hattori, Noriko; Bader, Hannah L.; Nelson, Courtney M.; Katebi, Negin; Matuska, Brittany; Olsen, Bjorn R.; Apte, Suneel S.
• Is Part Of: Genesis. Volume 52:Issue 7(2014:Jul.)
• Page Start: 702
• Page End: 712
• Publication Date: 2014-05-08
• Subjects: Developmental genetics -- Periodicals; Genetics -- Periodicals; Developmental biology -- Periodicals; Embryology -- Periodicals; Genetic regulation -- Periodicals; 576.5
• DOI: 10.1002/dvg.22784
• Languages: English
• ISSNs: 1526-954X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>ADAMTS9 is the most conserved member of a large family of secreted metalloproteases having diverse functions. <italic>Adamts9</italic> null mice die before gastrulation, precluding investigations of its roles later in embryogenesis, in adult mice or disease models. We therefore generated a floxed <italic>Adamts9</italic> allele to bypass embryonic lethality. In this mutant, unidirectional loxP sites flank exons 5–8, which encode the catalytic domain, including the protease active site. Mice homozygous for the floxed allele were viable, lacked an overt phenotype, and were fertile. Conversely, mice homozygous for a germ‐line deletion produced from the floxed allele by <italic>Cre</italic>‐lox recombination did not survive past gastrulation. Hemizygosity of the deleted <italic>Adamts9</italic> in combination with mutant <italic>Adamts20</italic> led to cleft palate and severe white spotting as previously described. Previously, <italic>Adamts9</italic> haploinsufficiency combined with either <italic>Adamts20</italic> or <italic>Adamts5</italic> nullizygosity suggested a cooperative role in interdigital web regression, but the outcome of deletion of <italic>Adamts9</italic> alone remained unknown. Here, <italic>Adamts9</italic> was conditionally deleted in limb mesoderm using <italic>Prx1</italic>‐Cre mice. Unlike other ADAMTS single knockouts, limb‐specific <italic>Adamts9</italic> deletion resulted in soft‐tissue syndactyly (STS) with 100% penetrance and concurrent deletion of <italic>Adamts5</italic> increased the severity of STS. Thus, <italic>Adamts9</italic> has both non‐redundant and cooperative roles in ensuring interdigital web regression. This new allele will be useful for investigating other biological functions of ADAMTS9. genesis 52:702–712, 2014. © 2014 Wiley Periodicals, Inc.</p> </abstract>