ArticlePloS one2010
An ADAMTSL2 founder mutation causes Musladin-Lueke Syndrome, a heritable disorder of beagle dogs, featuring stiff skin and joint contractures.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
- Comprehensive diagnosis and management of Musladin-Lueke Syndrome in a Beagle in Japan.The Journal of veterinary medical science · 2026Article
- The Pathogenic ADAMTSL2 D167N Variant Causes Geleophysic Dysplasia-Like Connective Tissue Changes in Mice.The American journal of pathology · 2026Article
- Myoblast-derived ADAMTS-like 2 promotes skeletal muscle regeneration after injury.NPJ Regenerative medicine · 2024Article
- Ethical Concerns about Fashionable Dog Breeding.Animals : an open access journal from MDPI · 2024Review
- Emerging roles for the ADAMTS-like family of matricellular proteins in cardiovascular disease through regulation of the extracellular microenvironment.Molecular biology reports · 2024Review
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- A nonsense mutation in mouse Adamtsl2 causes uterine hypoplasia and an irregular estrous cycle.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Article
- Secreted ADAMTS-like 2 promotes myoblast differentiation by potentiating WNT signaling.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Identification of Genomic Signatures in Bullmastiff Dogs Using Composite Selection Signals Analysis of 23 Purebred Clades.Animals : an open access journal from MDPI · 2023Article
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- The extracellular matrix glycoprotein ADAMTSL2 is increased in heart failure and inhibits TGFβ signalling in cardiac fibroblasts.Scientific reports · 2021Article
- Acromelic dysplasias: how rare musculoskeletal disorders reveal biological functions of extracellular matrix proteins.Annals of the New York Academy of Sciences · 2021Article
- ADAMTS9 and ADAMTS20 are differentially affected by loss of B3GLCT in mouse model of Peters plus syndrome.Human molecular genetics · 2019Article
- Limb- and tendon-specific Adamtsl2 deletion identifies a role for ADAMTSL2 in tendon growth in a mouse model for geleophysic dysplasia.Matrix biology : journal of the International Society for Matrix Biology · 2019Article
- Fell-Muir Lecture: Fibrillin microfibrils: structural tensometers of elastic tissues?International journal of experimental pathology · 2017Review
- Clinical Phenotype of Musladin-Lueke Syndrome in 2 Beagles.Journal of veterinary internal medicine · 2017Article
- ADAMTS proteins as modulators of microfibril formation and function.Matrix biology : journal of the International Society for Matrix Biology · 2015Review
- Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and bronchial epithelial dysplasia--a novel mouse model providing insights into geleophysic dysplasia.Disease models & mechanisms · 2015Article
- Genetic and functional linkage between ADAMTS superfamily proteins and fibrillin-1: a novel mechanism influencing microfibril assembly and function.Cellular and molecular life sciences : CMLS · 2011Review
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundMusladin-Lueke Syndrome (MLS) is a hereditary disorder affecting Beagle dogs that manifests with extensive fibrosis of the skin and joints. In this respect, it resembles human stiff skin syndrome and the Tight skin mouse, each of which is caused by gene defects affecting fibrillin-1, a major component of tissue microfibrils. The objective of this work was to determine the genetic basis of MLS and the molecular consequence of the identified mutation. METHODOLOGY AND PRINCIPAL
findingsWe mapped the locus for MLS by genome-wide association to a 3.05 Mb haplotype on canine chromosome 9 (CFA9 (50.11-54.26; p(raw) <10(-7))), which was homozygous and identical-by-descent among all affected dogs, consistent with recessive inheritance of a founder mutation. Sequence analysis of a candidate gene at this locus, ADAMTSL2, which is responsible for the human TGFβ dysregulation syndrome, Geleophysic Dysplasia (GD), uncovered a mutation in exon 7 (c.660C>T; p.R221C) perfectly associated with MLS (p-value=10(-12)). Murine ADAMTSL2 containing the p.R221C mutation formed anomalous disulfide-bonded dimers when transiently expressed in COS-1, HEK293F and CHO cells, and was present in the medium of these cells at lower levels than wild-type ADAMTSL2 expressed in parallel. CONCLUSIONS/SIGNIFICANCE: The genetic basis of MLS is a founder mutation in ADAMTSL2, previously shown to interact with latent TGF-β binding protein, which binds fibrillin-1. The molecular effect of the founder mutation on ADAMTSL2 is formation of disulfide-bonded dimers. Although caused by a distinct mutation, and having a milder phenotype than human GD, MLS nevertheless offers a new animal model for study of GD, and for prospective insights on mechanisms and pathways of skin fibrosis and joint contractures.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.