Phenotypes associated with this allele

• Allele Symbol: Fgf2^tm1Doe
• Allele Name: targeted mutation 1, Thomas Doetschman
• Allele ID: MGI:1857458
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fgf2^tm1Doe/Fgf2^tm1Doe	B6.129P2-Fgf2^tm1Doe	MGI:3763640
hm2	Fgf2^tm1Doe/Fgf2^tm1Doe	involves: 129P2/OlaHsd * Black Swiss	MGI:2679603
hm3	Fgf2^tm1Doe/Fgf2^tm1Doe	involves: 129P2/OlaHsd * C57BL/6	MGI:3763712
cx4	Fgf2^tm1Doe/Fgf2^tm1Doe Fgf9^tm1Dor/Fgf9^tm1Dor	involves: C57BL/6J	MGI:3529284

Genotype
MGI:3763640

hm1

• Allelic Composition: Fgf2^tm1Doe/Fgf2^tm1Doe
• Genetic Background: B6.129P2-Fgf2^tm1Doe

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

cardiovascular system

abnormal vascular endothelial cell migration ( J:114567 )

• following de-endothelialization and treatment with 17beta-Estradiol (E2), mice fail to re-endothelialize the site of injury unlike wild-type mice

• endothelial precursor cell migration in response to E2 is disrupted

cellular

abnormal vascular endothelial cell migration ( J:114567 )

• following de-endothelialization and treatment with 17beta-Estradiol (E2), mice fail to re-endothelialize the site of injury unlike wild-type mice

• endothelial precursor cell migration in response to E2 is disrupted

Genotype
MGI:2679603

hm2

• Allelic Composition: Fgf2^tm1Doe/Fgf2^tm1Doe
• Genetic Background: involves: 129P2/OlaHsd * Black Swiss

cardiovascular system

decreased cardiac muscle contractility ( J:119652 )

• recovery of contractile function in DMSO-treated heart following ischemia-reperfusion injury is decreased as compared to wild type (39 +/-4% vs 60 +/-7%)

• +dP/dt (derivative of change in contractile pressure over time) is decreased following ischemic-reperfusion injury in DMSO treated hearts

abnormal cardiac muscle relaxation ( J:119652 )

• -dP/dt (derivative of change in relaxation pressure over time) is increased as compared to wild type following ischemic-reperfusion injury in DMSO treated hearts

decreased left ventricle developed pressure ( J:45775 )

• 98.3+/-5.6 mmHg compared to 123.2+/-7.8 mmHg in wild-type mice

• maximal rate of ventricular contraction is decreased 7011.6+/-567 mmHg/s compared to 8631.6+/-746.6 mmHg/s in wild-type mice while maximum rate of ventricular relaxation is increased -7616.5+/-499.3 mmHg/s compared to -10716+/-713.8 mmHg/s in wild-type mice

decreased left ventricle systolic pressure ( J:119652 )

• LVSP is decreased as compared to wild type following ischemic-reperfusion injury in DMSO treated hearts

decreased mean systemic arterial blood pressure ( J:45775 )

• 78.0+/-5.9 mmHg compared to 98.9+/-5.6 mmHg in wild-type mice

decreased vasoconstriction ( J:45775 )

• in the portal vein spontaneous contractile activity and force generated are decreased

• however, sensitivity to phenylephrine and injury-induced vascular hyperplasia are normal

hematopoietic system

abnormal common myeloid progenitor cell morphology ( J:45775 )

• when cultured on methylcellulose bone marrow cells generate fewer IL-3-producing colonies and increased megakaryocyte colony-stimulating activity-induced megakaryocyte colonies compared to wild-type cells

• however, bone marrow cell culture response to granulocyte monocyte colony stimulating factor (GM-CSF) and erythropoietin, mitogen promoting granulocyte/macrophage and erythroid lineages, respectively, is normal

thrombocytosis ( J:45775 )

• 669+/-87x10³/mm³ compared to 472+/-68x10³/mm³ in wild-type mice

• however, platelet aggregation is normal

muscle

decreased cardiac muscle contractility ( J:119652 )

• recovery of contractile function in DMSO-treated heart following ischemia-reperfusion injury is decreased as compared to wild type (39 +/-4% vs 60 +/-7%)

• +dP/dt (derivative of change in contractile pressure over time) is decreased following ischemic-reperfusion injury in DMSO treated hearts

abnormal cardiac muscle relaxation ( J:119652 )

• -dP/dt (derivative of change in relaxation pressure over time) is increased as compared to wild type following ischemic-reperfusion injury in DMSO treated hearts

decreased vasoconstriction ( J:45775 )

• in the portal vein spontaneous contractile activity and force generated are decreased

• however, sensitivity to phenylephrine and injury-induced vascular hyperplasia are normal

increased cardiomyocyte apoptosis ( J:119652 )

• mice exhibit an increase TUNEL-positive cells (indicator of late stage apoptosis) in non-ischemic hearts as compared to wild-type

• following ischemia-reperfusion injury mice exhibit an increase TUNEL-positive cells (indicator of late stage apoptosis) in DMSO- treated hearts as compared to wild-type

nervous system

abnormal neuron morphology ( J:126973 )

• neuron density in the surpragranular layer is decreased by 60% compared to in wild-type mice

• mice exhibit a 45% decrease in SMI-32+ cell density in the infragranular layer with a decrease in neurophil staining of the frontal and parietal cortices

abnormal neuron differentiation ( J:126024 )

• neurogenesis following treatment with kainic acid or middle cerebral artery occlusion (MCAO) is less than in wild-type mice at days 9 and 16 post-treatment

• the number of proliferating cells following treatment with kainic acid is increased 2.4-fold compared to 6.8-fold in wild-type mice

• the number of proliferating cells following MCAO is increased 1.6-fold compared to 4.2-fold in wild-type mice

• the proportion of differentiating cells induced by kainic acid and MCAO reduced compared to in wild-type mice

• however, mice do not display an increase seizure following kainic acid treatment or difference in blood flow, mean arterial blood pressure or infarct size following MCAO

abnormal cerebral cortex pyramidal cell morphology ( J:126973 )

• pyramidal cell somata in the frontal and parietal cortices are smaller than in wild-type mice

• pyramidal cell dendritic staining is decreased compared to in wild-type mice

decreased cerebral cortex pyramidal cell number ( J:126973 )

• the number of pyramidal neurons in the cortex is decreased in all cortical layers

• however, the number of interneurons is unchanged

• no change in pyramidal or granule cell number is detected in the hippocampus

loss of glutamate neurons ( J:126973 )

• glutamate-immunoreactive cells in the dorsolateral prefrontal and parietal cortices are reduced in number

• however, glutamate cell density in the occipital cortex is normal

• the number of excitatory neurons (glutamate+) is decreased by 38% compared to in wild-type mice

• fewer glutamate staining cells are found in the entire cerebral cortex compared to in wild-type mice with anterior cortical region exhibiting a more pronounced lack than the posterior region

behavior/neurological

abnormal sleep duration ( J:126973 )

• in 3 to 4 month old male mice treated with PTB (a GABA receptor agonist), sleep time is increased (218+/-7 minutes compared to 159+/-904 minutes for wild-type mice)

• in 4 to 5 month old female mice treated with PTB (a GABA receptor agonist), sleep time is increased (118+/-19 minutes compared to 88+/-15 for wild-type mice)

cellular

increased cardiomyocyte apoptosis ( J:119652 )

• mice exhibit an increase TUNEL-positive cells (indicator of late stage apoptosis) in non-ischemic hearts as compared to wild-type

• following ischemia-reperfusion injury mice exhibit an increase TUNEL-positive cells (indicator of late stage apoptosis) in DMSO- treated hearts as compared to wild-type

abnormal neuron differentiation ( J:126024 )

• neurogenesis following treatment with kainic acid or middle cerebral artery occlusion (MCAO) is less than in wild-type mice at days 9 and 16 post-treatment

• the number of proliferating cells following treatment with kainic acid is increased 2.4-fold compared to 6.8-fold in wild-type mice

• the number of proliferating cells following MCAO is increased 1.6-fold compared to 4.2-fold in wild-type mice

• the proportion of differentiating cells induced by kainic acid and MCAO reduced compared to in wild-type mice

• however, mice do not display an increase seizure following kainic acid treatment or difference in blood flow, mean arterial blood pressure or infarct size following MCAO

Genotype
MGI:3763712

hm3

• Allelic Composition: Fgf2^tm1Doe/Fgf2^tm1Doe
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

cardiovascular system

abnormal response to cardiac infarction ( J:126804 )

• left ventricle chamber is increased 10-fold 4 weeks after infarct induction compared to wild-type mice in which dilation is 6-fold

• expansion index at 4 weeks post-infarct induction is twice as much as in wild-type mice

• following infarct induction mice exhibit less cardiomyocyte hypertrophy (4% increase in cross-section area compared to 19% increase in cross-section area in wild-type mice)

• fibroblast proliferation at 4 days and 1 week post-infarct induction is decreased 33% and 59%, respectively, compared to in wild-type mice

• interstitial fibrosis fails to increase as in wild-type mice after infarct induction

• the decline in vascular density declines more dramatically following myocardial infarct induction compared to in wild-type mice (74% versus 25% at week 1 week, 91% versus 75% at 4 weeks)

• following myocardial infarct induction, the average area per vessel is increased 10-fold compared to in wild-type mice (122.9+/-23.4 um² compared to 38.7+/-7.9 um² in wild-type mice and these large sinusoidal vessels often lack smooth muscle/pericyte investment

• however, vessel area is unchanged even after myocardial infarct induction

• following infarct induction, left ventricular function is decreased 20% compared to 11% in wild-type mice

increased myocardial infarct size ( J:126804 )

• cardiac infarcts fail to undergo scar contraction after 4 weeks as in wild-type mice

• however, there is no difference in infarct composition or initial size

homeostasis/metabolism

abnormal response to cardiac infarction ( J:126804 )

• left ventricle chamber is increased 10-fold 4 weeks after infarct induction compared to wild-type mice in which dilation is 6-fold

• expansion index at 4 weeks post-infarct induction is twice as much as in wild-type mice

• following infarct induction mice exhibit less cardiomyocyte hypertrophy (4% increase in cross-section area compared to 19% increase in cross-section area in wild-type mice)

• fibroblast proliferation at 4 days and 1 week post-infarct induction is decreased 33% and 59%, respectively, compared to in wild-type mice

• interstitial fibrosis fails to increase as in wild-type mice after infarct induction

• the decline in vascular density declines more dramatically following myocardial infarct induction compared to in wild-type mice (74% versus 25% at week 1 week, 91% versus 75% at 4 weeks)

• following myocardial infarct induction, the average area per vessel is increased 10-fold compared to in wild-type mice (122.9+/-23.4 um² compared to 38.7+/-7.9 um² in wild-type mice and these large sinusoidal vessels often lack smooth muscle/pericyte investment

• however, vessel area is unchanged even after myocardial infarct induction

• following infarct induction, left ventricular function is decreased 20% compared to 11% in wild-type mice

increased myocardial infarct size ( J:126804 )

• cardiac infarcts fail to undergo scar contraction after 4 weeks as in wild-type mice

• however, there is no difference in infarct composition or initial size

Genotype
MGI:3529284

cx4

• Allelic Composition: Fgf2^tm1Doe/Fgf2^tm1Doe; Fgf9^tm1Dor/Fgf9^tm1Dor
• Genetic Background: involves: C57BL/6J

cardiovascular system

increased heart atrium size ( J:95803 )

• at E12.5 the atria are enlarged

heart hypoplasia ( J:95803 )

• at E12.5, the hearts are smaller with a disproportionate loss of tissue at the apex of the heart and in the regions around the interventricular groove; however, the patterning of the ventricles, septum, valves, and outflow tract are normal

• double homozygotes are indistinguishable from Fgf9 single homozygotes