Disorder studied: Type 1 von Willebrand disease (T1-VWD).

Type of study: Translational

Model organism: Mouse (inbred strains) Obtained from Jackson Laboratory

Analyses:

VWF plasma protein quantitation (ELISA)

Hertiability calculations

PCR genotyping

QTL analysis

Allele-specific primer extension analysis

Results:

Identified new modifier of VWF known as (Mvwf5). Also found two loci unliked to Vwf known as (Mvwf6-7)

Mice with this variant displayed statistically significant decrease in VWF levels, recapitulating the decreasing patterns displayed in humans.

However, another strain of inbred mice with a different mutation did not show an age-dependent decrease in VWF. Suggests strain-specific differences in regulation of VWF levels over time.

Mvwf5 is a cis-regulatory variant altering Vwf mRNA expression.

This is a natural variant of the Vwf allele among inbred strains of mice. Found this variant causes elevation in steady-state levels of Vwf mRNA.

Authors state findings show equivalent of of type 1 VWD is remarkably common in mice and humans. ALso state the Mvwf1 analysis in wild mouse populations suggest this locus is under selective pressure.

Of the 5 potential modifier loci identified, 3 display conservation of synteny with potential human modifier loci.