Splice Variant of Spalax Heparanase Skipping Exon 12

Area of Science:

• Evolutionary Biology
• Molecular Biology
• Biochemistry

Background:

• The subterranean blind mole rat (Spalax) exhibits remarkable adaptations to its underground environment over 47 million years.
• Heparanase, an enzyme degrading heparan sulfate (HS) in the extracellular matrix (ECM), is crucial for Spalax's adaptation, promoting angiogenesis and growth factor release.

Purpose of the Study:

• To identify and characterize novel splice variants of heparanase in Spalax.
• To investigate the functional implications of these variants, particularly in response to environmental stimuli like hypoxia.

Main Methods:

• Analysis of kidney tissue samples from hypoxia-exposed Spalax.
• Molecular cloning and sequencing to identify splice variants.
• Assessment of enzymatic activity of the novel splice variant.

Main Results:

• A novel heparanase splice variant was identified in hypoxia-exposed Spalax kidney tissue, characterized by the skipping of exon 12.
• This variant maintains the correct translational reading frame.
• The novel splice variant demonstrated a lack of heparanase enzymatic activity.

Conclusions:

• The discovery of a non-enzymatic heparanase splice variant in Spalax provides new insights into the molecular mechanisms underlying its unique adaptations.
• This finding suggests alternative roles for heparanase variants beyond enzymatic degradation in Spalax evolution.