Phenotypes Associated with This Genotype

Genotype
MGI:3582488

• Allelic Composition: Rb1^tm1Tyj/Rb1^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:81082 , J:2511 )

• homozygous mutant embryos die between E14.5 and E15.5 (J:2511)

hematopoietic system

anemia ( J:2511 )

• at E13.5, homozygotes are severely pale relative to wild-type embryos

abnormal erythrocyte morphology ( J:2511 )

• in vitro, mutant erythroid precursors fail to reach end-stage differentiation: small hemaglobinized colonies from mutant mice are pale and contain increased numbers of small late normoblast-like cells instead of enucleated (mature) erythrocytes

• similarly, mutant large erythroid colonies are pale, with <5% enucleated erythrocytes relative to wild-type (45%)

abnormal erythropoiesis ( J:2511 )

• at E13.5, homozygotes display impaired definitive erythropoiesis and fail to produce sufficient numbers of mature erythrocytes, resulting in hypoxia and eventually death

low mean erythrocyte cell number ( J:2511 )

• at E13.5, wild-type embryos contain on average 45% enucleated, definitive erythrocytes; in contrast, mutant embryos only contain 6.8% enucleated cells

liver/biliary system

abnormal liver morphology ( J:2511 )

• at E13.5, mutant livers appear lacy and largely acellular; in contrast, wild-type livers are densely packed with cells (90% of which are of erythroid lineage)

small liver ( J:2511 )

• at E13.5, homozygotes display a slight reduction in liver size

homeostasis/metabolism

pericardial edema ( J:2511 )

• at E13.5, homozygotes display significant edema, particularly in the pericardial space

skin edema ( J:2511 )

• at E13.5, edema results in damage of the dermis and underlying mesenchyme

• however, most non-hematopoietic tissues remain unaffected until death (~E14.5)

cardiovascular system

pericardial edema ( J:2511 )

• at E13.5, homozygotes display significant edema, particularly in the pericardial space

nervous system

nervous system phenotype ( J:92520 )

N • normal numbers of primary neurospheres are produced from cultured E10 telencephalic neuroepithelia

increased neuron apoptosis ( J:2511 )

• at E12.5, mutant embryos exhibit increased neuronal apoptosis in the spinal cord, dorsal root ganglia and parts of the hindbrain

• neuronal cell death occurs prior to the manifestation of the erythropoietic defect, and does not appear to be a secondary effect of anemia-induced hypoxia

vision/eye

vision/eye phenotype ( J:2511 )

N • at E13.5, homozygotes display normal retinal development

cellular

increased apoptosis ( J:37145 )

• at E13.5, TUNEL analysis indicates a significant increase in apoptotic nuclei throughout the mutant nervous system (esp. dorsal ganglia), in skeletal muscle precursor cells (e.g. tongue myoblasts), lens, and to a lesser extent in liver

• in contrast, no significant increase in apoptosis is noted in the mutant lung or cardiac muscles

increased neuron apoptosis ( J:2511 )

• at E12.5, mutant embryos exhibit increased neuronal apoptosis in the spinal cord, dorsal root ganglia and parts of the hindbrain

• neuronal cell death occurs prior to the manifestation of the erythropoietic defect, and does not appear to be a secondary effect of anemia-induced hypoxia

increased cell proliferation ( J:81082 )

• MEFs largely fail to arrest in response to confluent growth and ~40% of the cells enter S phase

behavior/neurological

hunched posture ( J:37145 )

• at E13.5, 7 of 8 homozygotes display a hunchback posture

skeleton

abnormal cartilage morphology ( J:37145 )

• at E13.5, 7 of 8 homozygotes display a reduced cartilaginous frame (perichondrium) relative to wild-type mice

integument

skin edema ( J:2511 )

• at E13.5, edema results in damage of the dermis and underlying mesenchyme

• however, most non-hematopoietic tissues remain unaffected until death (~E14.5)