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.

Sefik, E., Israelow, B., Mirza, H., Zhao, J., Qu, R., Kaffe, E., Song, E., Halene, S., Meffre, E., Kluger, Y., Nussenzweig, M., Wilen, C. B., Iwasaki, A., & Flavell, R. A. (2021). A humanized mouse model of chronic COVID-19. Nature Biotechnology, 1–15. https://doi.org/10.1038/s41587-021-01155-4

H1 antihistamines enhance the opioid high in humans. Hospitals sometimes administer antihistamines in combination with opioids. It's not hard to find people online who are using this combination recreationally.