Cardiovascular Disease Mouse Models

Our catalog of KO mice contains numerous models displaying cardiovascular disease (CVD) phenotypes that you can appreciate, thanks to a panel of phenotyping tests mandated by the International Mouse Phenotyping Consortium (IMPC) and systematically performed on our lines.

Cardiovascular-related tests:

  • Heart weight: to evaluate cardiac size
  • Eye morphology: to detect blood vessel abnormalities
  • Electrocardiogram (ECG): to determine heart rate, potential ECG abnormalities and syndromes in a conscious mouse
  • Echocardiogram (echo): to assess the functionality of the heart (ejection fraction, stroke volume…) and identify potential mutant phenotypes

Examples of phenotyped KO lines with CVD phenotypes:

Aoc1, Cidec, Cisd2, Cybrd1, Epb41l5, Fbp2, Grm6, Gsto2, H2-M5, Il17rd, Mbtd1, Mybpc3, Myo10, Pcx, Pink1, Ric1, Ric8, Scarb1, Serf1, Tmem255b, Usp24, Vwa8, Zbtb24…

 

KO of genes associated with cardiovascular syndromes

Example 1:

In humans, a mutation for MYBPC3 gene, the cardiac isoform of myosin-binding protein C, is a cause of familial hypertrophic cardiomyopathy (1) KO mice for its murine homolog Mybpc3 show significant differences with WT in 4 tests including increased heart weight (observed during heart dissection)

Example 2:

Single nucleotide polyorphism in the human SCARB1, a plasma receptor for high density lipoprotein (HDL) cholesterol, contributes to genetic susceptibility to coronary heart disease (2). KO mice for Scarb1 show significant differences with WT in 6 tests including:

a) Increased rMSSD (root mean square of the successive differences) in Scrab1-/+ females (assessed by electrocardiogram)

b) Decreased cardiac muscle contractility in Scarb1-/- mice (quantified as lower fractional shortening by echo)

c, d) Expression data are also available for some lines, including Scarb1-/+ mice, showing LacZ expression in aorta and cartilage.


KO exhibiting abnormal heart rate, a phenotypic similarity to CVD

About 21 mouse lines KO for genes such as Abca7, Bbs5, Gja8, Ism2, Klhl29, Leprotl1, Lin28b, Mbd5, Pja2, and Uhrf2...

 

Example 3:

Decreased heart rate variability in transmembrane connexin protein Gja8-/- mice (ECG)

KO exhibiting abnormal retinal vasculature, a potential sign of high blood pressure, a phenotypic similarity to CVD

 

About 32 mouse lines KO for genes such as Anxa3, Cant1, Cyb561, Emc8, Fgfr1op, Mapt, Mfsd8, Ppfia2, Smoc1, and Wsb2...

 

Example 4:

Increased occurrence of abnormality in both eyes in integral membrane protein Mfsd8-/- mice (eye morphology)

References:

  1. Watkins, H. et al. Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy. Nat. Genet. 11, 434–7 (1995).
  2. Yoon, Y., Song, J., Hong, S. H. & Kim, J. Q. Analysis of multiple single nucleotide polymorphisms of candidate genes related to coronary heart disease susceptibility by using support vector machines. Clin Chem Lab Med 41, 529–534 (2003).