Phenotypes associated with this allele

• Allele Symbol: Wnt16^{tm2a(EUCOMM)Wtsi}
• Allele Name: targeted mutation 2a, Wellcome Trust Sanger Institute
• Allele ID: MGI:4840661
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Ldlr^tm1Her/Ldlr^tm1Her Wnt16^tm2a(EUCOMM)Wtsi/Wnt16^tm2a(EUCOMM)Wtsi	involves: 129S7/SvEvBrd * C57BL/6J * C57BL/6N	MGI:7861679

Genotype
MGI:7861679

cx1

• Allelic Composition: Ldlr^tm1Her/Ldlr^tm1Her; Wnt16^{tm2a(EUCOMM)Wtsi}/Wnt16^{tm2a(EUCOMM)Wtsi}
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J * C57BL/6N
• Cell Lines: EPD0561_6_A02

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

cardiovascular system

cardiovascular system phenotype ( J:344215 )

♂N • mice fed a Western high fat diet (HFD) for 10 months show a non-significant 40% reduction in aortic calcium accrual relative to HFD-fed single Ldlr^tm1Her homozygous controls

abnormal aorta tunica media morphology ( J:344215 )

♂ • mice show disorganized morphology in the tunica media of the ascending aorta relative to single Ldlr^tm1Her homozygous controls

abnormal aorta elastic tissue morphology ( J:344215 )

♂ • after AngII + HFD challenge, mice show significantly less AngII-induced elastin breaks in the thoracic ascending aorta (TAA) tunica media than similarly challenged single Ldlr^tm1Her homozygous controls

♂ • however, TAA wall thickness remains unaffected

abnormal aorta smooth muscle morphology ( J:344215 )

♂ • TEM of ascending aorta tissue shows abnormal aortic vascular smooth muscle (VSM) morphology, most pronounced in the inner tunica media

abnormal ascending aorta morphology ( J:344215 )

♂

increased susceptibility to induced aneurysm formation ( J:344215 )

♂ • after AngII + HFD challenge, mice show an additional 20% increase in TAA diameter relative to similarly challenged single Ldlr^tm1Her homozygous controls, with strong trends for larger aortic diameters noted in the aortic arch between innominate and left carotid arteries and in the widest abdominal aorta segment

♂ • however, the overall mortality due to aortic rupture (23%) is similar to that in controls

♂ • no differences in TAA diameter are noted at baseline (without AngII + HFD challenge) or after 10 months of HFD alone

decreased systemic arterial systolic blood pressure ( J:344215 )

♂ • mice show significantly lower baseline systolic blood pressure than single Ldlr^tm1Her homozygous controls

abnormal blood vessel physiology ( J:344215 )

♂ • mice show a strong trend towards reduced aortic pulse wave velocity (PWV), an index of arterial stiffness, relative to single Ldlr^tm1Her homozygous controls

♂ • a significant reduction in aortic PWV is observed after AngII + HFD challenge

abnormal vascular smooth muscle physiology ( J:344215 )

♂ • in culture, primary VSM cells isolated from the thoracic aorta show lower mRNA levels of contractile VSM markers (Acta2, Myh11, and Myocd) with concomitant upregulation of VSM dedifferentiation markers (Ly6a/Sca1, C3, and C4b)

♂ • primary aortic VSM cultures show significantly less accumulation of contractile proteins (ACTA2, SM22, and MYH11) along with increased complement C3 protein production

♂ • after AngII + HFD challenge, thoracic aortic extracts show markedly reduced protein levels of ANKRD1 (ankyrin repeat domain 1), a prototypic contractile target of Yap1/Wwtr1 transcription

♂ • cultured aortic VSM cells show reduced nuclear and increased cytoplasmic accumulation of Yap1 and Wwtr1

decreased vasoconstriction ( J:344215 )

♂ • in a floating matrix gel contraction assay, Tgfb1-induced aortic VSM contraction is significantly reduced to 21% (versus 45% in control cells), with a floating gel area that is 33% larger than in Tgfb1-stimulated control cells

muscle

abnormal aorta smooth muscle morphology ( J:344215 )

♂ • TEM of ascending aorta tissue shows abnormal aortic vascular smooth muscle (VSM) morphology, most pronounced in the inner tunica media

abnormal vascular smooth muscle physiology ( J:344215 )

♂ • in culture, primary VSM cells isolated from the thoracic aorta show lower mRNA levels of contractile VSM markers (Acta2, Myh11, and Myocd) with concomitant upregulation of VSM dedifferentiation markers (Ly6a/Sca1, C3, and C4b)

♂ • primary aortic VSM cultures show significantly less accumulation of contractile proteins (ACTA2, SM22, and MYH11) along with increased complement C3 protein production

♂ • after AngII + HFD challenge, thoracic aortic extracts show markedly reduced protein levels of ANKRD1 (ankyrin repeat domain 1), a prototypic contractile target of Yap1/Wwtr1 transcription

♂ • cultured aortic VSM cells show reduced nuclear and increased cytoplasmic accumulation of Yap1 and Wwtr1

decreased vasoconstriction ( J:344215 )

♂ • in a floating matrix gel contraction assay, Tgfb1-induced aortic VSM contraction is significantly reduced to 21% (versus 45% in control cells), with a floating gel area that is 33% larger than in Tgfb1-stimulated control cells

abnormal muscle fiber mitochondrial morphology ( J:344215 )

♂ • mice show abnormal VSM mitochondrial morphology in the ascending aorta; mitochondria appear swollen and display a more homogeneous electron-dense mitochondrial matrix with indistinct cristae

cellular

abnormal mitochondrial crista morphology ( J:344215 )

♂ • VSM mitochondria exhibit indistinct cristae in the ascending aorta, unlike mitochondria in single Ldlr^tm1Her homozygous controls which have distinct bar-like cristae

abnormal mitochondrial matrix morphology ( J:344215 )

♂ • VSM mitochondria exhibit a more homogeneous electron-dense mitochondrial matrix in the ascending aorta

abnormal muscle fiber mitochondrial morphology ( J:344215 )

♂ • mice show abnormal VSM mitochondrial morphology in the ascending aorta; mitochondria appear swollen and display a more homogeneous electron-dense mitochondrial matrix with indistinct cristae

dilated mitochondrion ( J:344215 )

♂ • VSM mitochondria appear swollen in the ascending aorta, unlike in single Ldlr^tm1Her homozygous controls

abnormal mitochondrial physiology ( J:344215 )

♂ • in a mitochondrial stress test, aortic VSM mitochondria show significantly decreased basal and maximal oxygen consumption and a lower VSM spare respiratory capacity than control VSM mitochondria

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:344215 )

♂N • mice fed a HFD for 3 or 10 months show no significant changes in fasting plasma cholesterol levels relative to similarly HFD-fed single Ldlr^tm1Her homozygous controls

♂N • after angiotensin-II (AngII) infusion, HFD-fed mice show no differences in fasting plasma cholesterol levels relative to AngII + HFD challenged single Ldlr^tm1Her homozygous controls

increased circulating aldosterone level ( J:344215 )

♂ • mice show significantly higher serum aldosterone levels than single Ldlr^tm1Her homozygous controls