Phenotypes associated with this allele

• Allele Symbol: Grem2^tm1Akh
• Allele Name: targeted mutation 1, Antonios Hatzopoulos
• Allele ID: MGI:6343527
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Grem2^tm1Akh/Grem2^tm1Akh	involves: 129/Sv * C57BL/6	MGI:6763953

Genotype
MGI:6763953

hm1

• Allelic Composition: Grem2^tm1Akh/Grem2^tm1Akh
• Genetic Background: involves: 129/Sv * C57BL/6

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

cardiovascular system

cardiovascular system phenotype ( J:250034 )

N • no major structural or physiological defects or alterations in heart size, cardiac tissue morphology and cardiac function at 12 weeks of age under baseline conditions

decreased heart left ventricle muscle contractility ( J:250034 )

• worsened cardiac function with lower fractional shortening and ejection fraction values and higher systolic left ventricular internal diameters than wild-type controls at days 7 and 21 post MI

increased heart rate ( J:250034 )

• small increase in heart rate relative to wild-type controls

abnormal response to myocardial ischemic injury ( J:250034 )

• enhanced expression of proinflammatory genes in endothelial cells in and around the injury site after myocardial infarction (MI) by permanent ligation of the left anterior descending coronary artery

• higher induction levels of genes encoding endothelial cell-specific adhesion membrane proteins, Sele (E-selectin), Vcam1 and Icam1, at days 2 and 7 post MI; however, expression levels are comparable to wild-type levels by day 21 post MI

• endothelial cells within the infarct and peri-infarct areas stain positively for E-selectin protein at day 7 post MI, unlike in wild-type hearts

• 3-fold increase in infiltrating inflammatory CD45+ leukocytes in the heart at day 5 post MI

• 2-3-fold increase in Ly6C^hi cells (mostly monocytes), neutrophils (Ly6G+), T cells (CD3+) and macrophages (F4/80+), with a similar increase in proinflammatory F4/80+ macrophages expressing high levels of Ly6C (F4/80+/Ly6C^hi), the monocyte chemoattractant protein-1 (or Ccl2) receptor Ccr2 (F4/80+/Ccr2^hi), or both (F4/80+/Ly6C^hi/Ccr2^hi) at day 5 post MI

• higher induction levels of Tgfbeta1 and Il10 in the heart at day 7 post MI

• however, initial infarct sizes are similar those in wild-type controls at day 1 post MI

immune system

increased leukocyte cell number ( J:250034 )

• 3-fold increase in infiltrating inflammatory CD45+ leukocytes in the heart at day 5 post MI

• ~2-fold increase in the number of circulating leukocytes at day 5 post MI

• however, normal leukocyte numbers in the blood at baseline

abnormal chemokine level ( J:250034 )

• moderate (1.7-fold) increase in chemokine Ccl2 [chemokine (C-C motif) ligand 2] expression at day 2 after MI

increased interleukin-10 secretion ( J:250034 )

• higher induction levels of Il10 in the heart at day 7 post MI, but dropping to normal levels by day 21

increased inflammatory response ( J:250034 )

• increased inflammatory cell infiltration in the heart after myocardial infarction (MI) at day 5 post MI; however, duration of the inflammatory response is normal with CD45+, Ly6C+ and F4/80+ cell numbers returning close to baseline levels at day 14 post MI, as seen in wild-type controls

• excessive inflammation is due to increased p-Smad1/5/8 BMP mediated signaling in peri-infarct area cardiomyocytes, as treatment with DMH1 (the canonical BMP-signaling inhibitor) rescues the pro-inflammatory phenotype and causes a dramatic decrease in infiltrated CD45+, Ly6C+, and F4/80+ cells at day 5 post MI

homeostasis/metabolism

abnormal response to myocardial ischemic injury ( J:250034 )

• enhanced expression of proinflammatory genes in endothelial cells in and around the injury site after myocardial infarction (MI) by permanent ligation of the left anterior descending coronary artery

• higher induction levels of genes encoding endothelial cell-specific adhesion membrane proteins, Sele (E-selectin), Vcam1 and Icam1, at days 2 and 7 post MI; however, expression levels are comparable to wild-type levels by day 21 post MI

• endothelial cells within the infarct and peri-infarct areas stain positively for E-selectin protein at day 7 post MI, unlike in wild-type hearts

• 3-fold increase in infiltrating inflammatory CD45+ leukocytes in the heart at day 5 post MI

• 2-3-fold increase in Ly6C^hi cells (mostly monocytes), neutrophils (Ly6G+), T cells (CD3+) and macrophages (F4/80+), with a similar increase in proinflammatory F4/80+ macrophages expressing high levels of Ly6C (F4/80+/Ly6C^hi), the monocyte chemoattractant protein-1 (or Ccl2) receptor Ccr2 (F4/80+/Ccr2^hi), or both (F4/80+/Ly6C^hi/Ccr2^hi) at day 5 post MI

• higher induction levels of Tgfbeta1 and Il10 in the heart at day 7 post MI

• however, initial infarct sizes are similar those in wild-type controls at day 1 post MI

abnormal chemokine level ( J:250034 )

• moderate (1.7-fold) increase in chemokine Ccl2 [chemokine (C-C motif) ligand 2] expression at day 2 after MI

increased transforming growth factor beta level ( J:250034 )

• higher induction levels of Tgfbeta1 in the heart at day 7 post MI, but dropping to normal levels by day 21

hematopoietic system

increased leukocyte cell number ( J:250034 )

• 3-fold increase in infiltrating inflammatory CD45+ leukocytes in the heart at day 5 post MI

• ~2-fold increase in the number of circulating leukocytes at day 5 post MI

• however, normal leukocyte numbers in the blood at baseline

muscle

decreased heart left ventricle muscle contractility ( J:250034 )

• worsened cardiac function with lower fractional shortening and ejection fraction values and higher systolic left ventricular internal diameters than wild-type controls at days 7 and 21 post MI