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Ligneous membranitis in Scottish Terriers is associated with a single nucleotide polymorphism in the plasminogen
Stuart Ainsworth1, Stuart Carter1, Claire Fisher2
1Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, ic2 Building, Liverpool, L3 5RF, UK.
Abstract:
Ligneous membranitis (LM) is a rare chronic inflammatory condition of the mucous membranes associated with plasminogen (encoded by PLG) deficiency in affected humans and dogs. In human, the condition is genetic in nature with numerous mutations and polymorphisms in PLG identified in affected individuals and related family members. The condition is uncommonly reported in dogs and, to date, no genetic studies have been performed. We identified related Scottish Terriers (littermates) with severe LM and unaffected relatives (sire, dam and a sibling from a previous litter). Plasma plasminogen activity was below normal in one affected dog but within normal reference intervals for the other. Sequencing of PLG from the affected dogs revealed a homozygous A>T single nucleotide polymorphism in an intron donor site (c.1256+2T>A). The related, unaffected dogs displayed heterozygous alleles at this position (c.1256+2T/A), whereas no mutation was detected in unaffected, non-related control dogs. This is the first report to identify gene polymorphisms associated with LM in dogs.
Insights
Ligneous membranitis (LM) in Scottish Terriers is linked to plasminogen (PLG) gene variations. This study identifies a specific PLG polymorphism associated with the rare inflammatory condition in dogs.
Area of Science:
- Veterinary Genetics
- Canine Pathology
- Molecular Biology
Background:
- Ligneous membranitis (LM) is a rare, chronic inflammatory disease affecting mucous membranes.
- LM is associated with plasminogen (PLG) deficiency in humans and dogs.
- Genetic factors are implicated in human LM, but canine LM genetics remain unstudied.
Purpose of the Study:
- To investigate the genetic basis of ligneous membranitis in Scottish Terriers.
- To identify potential mutations or polymorphisms in the PLG gene associated with LM in dogs.
Main Methods:
- Identified affected Scottish Terriers and their relatives (littermates, parents).
- Measured plasma plasminogen activity in affected and unaffected dogs.
- Sequenced the PLG gene in affected dogs and related unaffected dogs.
Main Results:
- Identified a homozygous A>T single nucleotide polymorphism (c.1256+2T>A) in the PLG gene of affected dogs.
- Unaffected relatives showed heterozygous alleles (c.1256+2T/A) at this locus.
- No mutation was found in unrelated control dogs, suggesting a genetic link.
Conclusions:
- This is the first report identifying a specific gene polymorphism associated with ligneous membranitis in dogs.
- The identified PLG polymorphism is strongly associated with LM in the Scottish Terrier breed.
- Further research into canine PLG genetics can inform diagnosis and potential therapeutic strategies.
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