Phenotypes Associated with This Genotype

Genotype
MGI:4936843

• Allelic Composition: Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan; Tg(Tek-cre)12Flv/0
• Genetic Background: B6.Cg-Rb1cc1^tm1.1Guan Tg(Tek-cre)12Flv

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

mortality/aging

postnatal lethality, complete penetrance ( J:167258 )

• all mice die within the first week of birth

lethality throughout fetal growth and development, incomplete penetrance ( J:167258 )

• slight decrease in the number of expected embryos observed at E17.5 and E18.5

hematopoietic system

increased hematopoietic stem cell proliferation ( J:167258 )

• hematopoietic stem cells (HSCs) exhibit increased rate of proliferation, but no differences in apoptosis, compared to wild-type HSCs

abnormal erythropoiesis ( J:167258 )

• fetal erythropoiesis is impaired in mutants by E16.5, with very few erythrocytes within vascular structures

• at E14.5, marker analysis indicates that mutants exhibit an increase in frequency of immature erythroid cells and a reduction in the absolute number of maturing erythroid cells, suggesting that erythroid maturation is compromised

abnormal myelopoiesis ( J:167258 )

• E14.5 fetal liver exhibits a more than 4-fold increase in the number of myeloid lineage cells, indicating enhanced myelopoiesis

anemia ( J:167258 )

• severe erythroblastic anemia

increased erythroblast number ( J:167258 )

• increase in numbers of erythroblasts in the peripheral blood at E18.5

decreased erythrocyte cell number ( J:167258 )

• at E18.5

decreased hematocrit ( J:167258 )

• at E18.5

decreased hemoglobin content ( J:167258 )

• at E18.5

increased red blood cell distribution width ( J:167258 )

• at E18.5

increased neutrophil cell number ( J:167258 )

• in peripheral blood at E18.5

decreased hematopoietic stem cell number ( J:167258 )

• 6-fold lower frequency of immunophenotypic HSCs in fetal livers at E14.5; competitive reconstitution experiments confirm the reduction in HSCs and that HSCs simply do not change their immunephenotype in mut

liver/biliary system

abnormal liver morphology ( J:167258 )

• decrease in total fetal liver cell number at E14.5, with further decreases at E18.5

pale liver ( J:167258 )

• at E16.5 and E18.5

cellular

abnormal mitochondrial morphology ( J:167258 )

• fetal liver cells at E14.5 exhibit an increase in mitochondrial mass

abnormal autophagy ( J:167258 )

• mutants exhibit an accumulation of p62, a selective substrate for autophagy, and a 50% increase in ROS levels in fetal cells, indicating a defect in autophagy in fetal liver cells

increased hematopoietic stem cell proliferation ( J:167258 )

• hematopoietic stem cells (HSCs) exhibit increased rate of proliferation, but no differences in apoptosis, compared to wild-type HSCs

immune system

abnormal myelopoiesis ( J:167258 )

• E14.5 fetal liver exhibits a more than 4-fold increase in the number of myeloid lineage cells, indicating enhanced myelopoiesis

increased neutrophil cell number ( J:167258 )

• in peripheral blood at E18.5

cardiovascular system

cardiovascular system phenotype ( J:167258 )

N • hemorrhaging is not observed even though the cre transgene is expressed in endothelial cells

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:167258 )

N • edema is not observed even though the cre transgene is expressed in endothelial cells

abnormal autophagy ( J:167258 )

• mutants exhibit an accumulation of p62, a selective substrate for autophagy, and a 50% increase in ROS levels in fetal cells, indicating a defect in autophagy in fetal liver cells