Phenotypes associated with this allele

• Allele Symbol: Cbfb^tm1Spe
• Allele Name: targeted mutation 1, Nancy A Speck
• Allele ID: MGI:1934195
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cbfb^tm1Spe/Cbfb^tm1Spe	either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)	MGI:3588736
ht2	Cbfb^tm1Spe/Cbfb^tm2.1Spe	involves: 129S4/SvJae	MGI:3721372
cx3	Cbfb^tm1Spe/Cbfb^tm1Spe Tg(Tek-GFP/Cbfb)1Spe/0	either: (involves: 129S4/SvJae * BALB/c * CD-1) or (involves: 129S4/SvJae * C57BL/6 * CD-1)	MGI:2653200
cx4	Cbfb^tm1Spe/Cbfb^tm1Spe Tg(Tek-GFP/Cbfb)2Spe/0	either: (involves: 129S4/SvJae * BALB/c * CD-1 * Swiss Webster) or (involves: 129S4/SvJae * C57BL/6 * CD-1 * Swiss Webster)	MGI:2653204

Genotype
MGI:3588736

hm1

• Allelic Composition: Cbfb^tm1Spe/Cbfb^tm1Spe
• Genetic Background: either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:36593 )

• homozygotes die between E11.5 and E14.5

cardiovascular system

abnormal capillary morphology ( J:36593 )

• at E10.5, apoptosis and perivascular edema appear to be associated with sprouting and/or anastomosing capillaries of the affected region

hemorrhage ( J:36593 )

• at E10.5, homozygotes exhibit extensive hemorrhages predominantly in the CNS

intracranial hemorrhage ( J:36593 )

• at E11.5, homozygotes display segmental bleeds in the areas corresponding to the VII/VIII cranial nerve complex

intraventricular hemorrhage ( J:36593 )

• at E11.5, homozygotes exhibit hemorrhages in the lateral, third and fourth ventricles

spinal hemorrhage ( J:36593 )

• at E11.5, homozygotes display hemorrhagic lesions in intersegmental regions along the presumptive spinal cord

nervous system

intracranial hemorrhage ( J:36593 )

• at E11.5, homozygotes display segmental bleeds in the areas corresponding to the VII/VIII cranial nerve complex

intraventricular hemorrhage ( J:36593 )

• at E11.5, homozygotes exhibit hemorrhages in the lateral, third and fourth ventricles

spinal hemorrhage ( J:36593 )

• at E11.5, homozygotes display hemorrhagic lesions in intersegmental regions along the presumptive spinal cord

cellular

increased apoptosis ( J:36593 )

• at E10.5, homozygotes exhibit increased apoptosis in hemorrhagic lesions of the CNS and in cephalic mesodermal tissue

• apoptosis or necrosis appears to precede hemorrhaging in affected sites

homeostasis/metabolism

edema ( J:36593 )

• at E10.5, homozygotes display perivascular edema

hematopoietic system

impaired hematopoiesis ( J:36593 )

• homozygotes exhibit impaired fetal liver hematopoiesis; in contrast, primitive yolk-sac derived hematopoiesis is unaffected

• at E12.5, mutant fetal livers lack blood precursor cells in the sinusoids; instead, primary nucleated yolk-sac derived erythrocytes are present and only a few hematopoietic precursors are found

abnormal myeloblast morphology/development ( J:36593 )

• at E12.5, the number of blast-like progenitors of definitive erythroid and myeloid cells is ~100-fold lower in mutant livers relative to wild-type

decreased erythroblast number ( J:36593 )

• at E12.5, homozygotes contain severely reduced definitive erythroblasts in peripheral blood

Genotype
MGI:3721372

ht2

• Allelic Composition: Cbfb^tm1Spe/Cbfb^tm2.1Spe
• Genetic Background: involves: 129S4/SvJae

mortality/aging

neonatal lethality, complete penetrance ( J:124224 )

• die within the first day after birth although born at normal Mendelian ratios

skeleton

abnormal limb bone morphology ( J:124224 )

abnormal phalanx morphology ( J:124224 )

abnormal metacarpal bone morphology ( J:124224 )

abnormal metatarsal bone morphology ( J:124224 )

abnormal long bone diaphysis morphology ( J:124224 )

• reduced primary ossification and delayed appearance of secondary ossification centers

• increased severity

abnormal pectoral girdle bone morphology ( J:124224 )

abnormal clavicle morphology ( J:124224 )

abnormal scapula morphology ( J:124224 )

abnormal axial skeleton morphology ( J:124224 )

abnormal cranium morphology ( J:124224 )

abnormal neurocranium morphology ( J:124224 )

abnormal mandible morphology ( J:124224 )

abnormal maxilla morphology ( J:124224 )

abnormal sternum morphology ( J:124224 )

abnormal rib morphology ( J:124224 )

abnormal skeleton development ( J:124224 )

• delayed ossification of ribs, metacarpal/metatarsal bones, phalanges, pelvis, sternum, vertebrae

• hypoplastic clavicles, scapulae, calvaria, maxillae, mandibles

• increased severity

abnormal vertebrae development ( J:124224 )

hematopoietic system

abnormal thymus morphology ( J:124224 )

abnormal thymus cell ratio ( J:124224 )

• lower percentage of double positive T cells and absolute numbers reduced 100 fold

• increased levels of CD4 expressing cells

thymus hypoplasia ( J:124224 )

• small size

• reduced cellularity

abnormal T cell differentiation ( J:124224 )

• transition from early T-lineage to DN2 stage severely impaired

• DN2 to DN3 transition severely impaired

decreased double-positive T cell number ( J:124224 )

• lower percentage of double positive T cells and absolute numbers reduced 100 fold

extramedullary hematopoiesis ( J:124224 )

• half the number of hematopoietic cells in the fetal liver at E12.5

• reversed at E17.5

abnormal megakaryocyte morphology ( J:124224 )

• colonies in culture are denser with smaller cells

thrombocytopenia ( J:124224 )

• reduced numbers of platelets both in culture and in the circulation

increased CD4-positive, alpha-beta T cell number ( J:124224 )

• increased levels of CD4 expressing T cells but not typical CD4+ cells

abnormal splenic cell ratio ( J:124224 )

• 4-5 fold reduction in CD45⁺ numbers

• 10-20 fold reduction in monocyte/granulocytes

• CD19⁺ B cells and Ter119 erythrocyte numbers are reduced but proportionally normal

immune system

abnormal thymus morphology ( J:124224 )

abnormal thymus cell ratio ( J:124224 )

• lower percentage of double positive T cells and absolute numbers reduced 100 fold

• increased levels of CD4 expressing cells

thymus hypoplasia ( J:124224 )

• small size

• reduced cellularity

abnormal T cell differentiation ( J:124224 )

• transition from early T-lineage to DN2 stage severely impaired

• DN2 to DN3 transition severely impaired

decreased double-positive T cell number ( J:124224 )

• lower percentage of double positive T cells and absolute numbers reduced 100 fold

increased CD4-positive, alpha-beta T cell number ( J:124224 )

• increased levels of CD4 expressing T cells but not typical CD4+ cells

abnormal splenic cell ratio ( J:124224 )

• 4-5 fold reduction in CD45⁺ numbers

• 10-20 fold reduction in monocyte/granulocytes

• CD19⁺ B cells and Ter119 erythrocyte numbers are reduced but proportionally normal

craniofacial

abnormal cranium morphology ( J:124224 )

abnormal neurocranium morphology ( J:124224 )

abnormal mandible morphology ( J:124224 )

abnormal maxilla morphology ( J:124224 )

limbs/digits/tail

abnormal limb bone morphology ( J:124224 )

abnormal phalanx morphology ( J:124224 )

abnormal metacarpal bone morphology ( J:124224 )

abnormal metatarsal bone morphology ( J:124224 )

endocrine/exocrine glands

abnormal thymus morphology ( J:124224 )

abnormal thymus cell ratio ( J:124224 )

• lower percentage of double positive T cells and absolute numbers reduced 100 fold

• increased levels of CD4 expressing cells

thymus hypoplasia ( J:124224 )

• small size

• reduced cellularity

Genotype
MGI:2653200

cx3

• Allelic Composition: Cbfb^tm1Spe/Cbfb^tm1Spe; Tg(Tek-GFP/Cbfb)1Spe/0
• Genetic Background: either: (involves: 129S4/SvJae * BALB/c * CD-1) or (involves: 129S4/SvJae * C57BL/6 * CD-1)

cellular

abnormal osteoblast differentiation ( J:80670 )

• bone collar shows few differentiating osteoblasts

mortality/aging

perinatal lethality, complete penetrance ( J:80670 )

• die at birth

craniofacial

protruding tongue ( J:80670 )

short snout ( J:80670 )

hematopoietic system

small thymus ( J:80670 )

• thymus is small and contains 50% fewer cells than in wild-type

abnormal definitive hematopoiesis ( J:80670 )

abnormal common myeloid progenitor cell morphology ( J:80670 )

• fetal livers contain 50% as many colony forming unit (CFU)-granulocyte/erythroid/monocyte/macrophage (GEMM) progenitors as do wild-type

abnormal erythropoiesis ( J:80670 )

• overall increase in the proportion of red blood cell precursors from 38% to 79% of nucleated cells at E17.5

abnormal myelopoiesis ( J:80670 )

• few mature myeloid cells are present

increased erythroid progenitor cell number ( J:80670 )

• ratio of erythroid precursors to myeloid precursors is increased from 0.48 in wild-type fetuses to 1.22 in mutant fetuses at E17.5

increased CD4-positive, alpha-beta T cell number ( J:80670 )

• increase in numbers of single CD4+ cells in thymuses

increased hematopoietic stem cell number ( J:80670 )

• 2-fold increase in hematopoietic progenitors

spleen hypoplasia ( J:80670 )

• spleens are hypocellular, but overall structure and organization is normal

abnormal splenic cell ratio ( J:80670 )

• fewer B220+ cells, GR-1+ neutrophils and Mac-1+ cells in E17.5 spleens

immune system

small thymus ( J:80670 )

• thymus is small and contains 50% fewer cells than in wild-type

abnormal myelopoiesis ( J:80670 )

• few mature myeloid cells are present

increased CD4-positive, alpha-beta T cell number ( J:80670 )

• increase in numbers of single CD4+ cells in thymuses

spleen hypoplasia ( J:80670 )

• spleens are hypocellular, but overall structure and organization is normal

abnormal splenic cell ratio ( J:80670 )

• fewer B220+ cells, GR-1+ neutrophils and Mac-1+ cells in E17.5 spleens

skeleton

abnormal osteoblast differentiation ( J:80670 )

• bone collar shows few differentiating osteoblasts

bowed tibia ( J:80670 )

abnormal long bone hypertrophic chondrocyte zone ( J:80670 )

delayed chondrocyte differentiation ( J:80670 )

• delay in chondrocyte maturation

delayed bone ossification ( J:80670 )

• ossification of the limbs, ribs and vertebra is delayed at E17.5

delayed endochondral bone ossification ( J:80670 )

delayed intramembranous bone ossification ( J:80670 )

• intramembranous bone formation is initiated but is either prematurely terminated or delayed at an early stage of osteoblast differentiation

vision/eye

eyelids open at birth ( J:80670 )

• delay in or incomplete closure of the eyelids

digestive/alimentary system

protruding tongue ( J:80670 )

limbs/digits/tail

bowed tibia ( J:80670 )

short limbs ( J:80670 )

liver/biliary system

abnormal liver morphology ( J:80670 )

• decrease in the percentage of CD19+ and B220+ B cells, GR1+ neutrophils and Mac-1+ cells in fetal liver

endocrine/exocrine glands

small thymus ( J:80670 )

• thymus is small and contains 50% fewer cells than in wild-type

growth/size/body

protruding tongue ( J:80670 )

short snout ( J:80670 )

Genotype
MGI:2653204

cx4

• Allelic Composition: Cbfb^tm1Spe/Cbfb^tm1Spe; Tg(Tek-GFP/Cbfb)2Spe/0
• Genetic Background: either: (involves: 129S4/SvJae * BALB/c * CD-1 * Swiss Webster) or (involves: 129S4/SvJae * C57BL/6 * CD-1 * Swiss Webster)

cellular

abnormal osteoblast differentiation ( J:80670 )

• bone collar shows few differentiating osteoblasts

mortality/aging

perinatal lethality, complete penetrance ( J:80670 )

• die at birth

craniofacial

protruding tongue ( J:80670 )

short snout ( J:80670 )

hematopoietic system

small thymus ( J:80670 )

• thymus is small and contains 50% fewer cells than in wild-type

abnormal definitive hematopoiesis ( J:80670 )

abnormal common myeloid progenitor cell morphology ( J:80670 )

• fetal livers contain 50% as many colony forming unit (CFU)-granulocyte/erythroid/monocyte/macrophage (GEMM) progenitors as do wild-type

abnormal erythropoiesis ( J:80670 )

• overall increase in the proportion of red blood cell precursors from 38% to 79% of nucleated cells at E17.5

abnormal myelopoiesis ( J:80670 )

• few mature myeloid cells are present

increased erythroid progenitor cell number ( J:80670 )

• ratio of erythroid precursors to myeloid precursors is increased from 0.48 in wild-type fetuses to 1.22 in mutant fetuses at E17.5

increased CD4-positive, alpha-beta T cell number ( J:80670 )

• increase in numbers of single CD4+ cells in thymuses

increased hematopoietic stem cell number ( J:80670 )

• 2-fold increase in hematopoietic progenitors

spleen hypoplasia ( J:80670 )

• spleens are hypocellular, but overall structure and organization is normal

abnormal splenic cell ratio ( J:80670 )

• fewer B220+ cells, GR-1+ neutrophils and Mac-1+ cells in E17.5 spleens

immune system

small thymus ( J:80670 )

• thymus is small and contains 50% fewer cells than in wild-type

abnormal myelopoiesis ( J:80670 )

• few mature myeloid cells are present

increased CD4-positive, alpha-beta T cell number ( J:80670 )

• increase in numbers of single CD4+ cells in thymuses

spleen hypoplasia ( J:80670 )

• spleens are hypocellular, but overall structure and organization is normal

abnormal splenic cell ratio ( J:80670 )

• fewer B220+ cells, GR-1+ neutrophils and Mac-1+ cells in E17.5 spleens

skeleton

abnormal osteoblast differentiation ( J:80670 )

• bone collar shows few differentiating osteoblasts

bowed tibia ( J:80670 )

abnormal long bone hypertrophic chondrocyte zone ( J:80670 )

delayed chondrocyte differentiation ( J:80670 )

• delay in chondrocyte maturation

delayed bone ossification ( J:80670 )

• ossification of the limbs, ribs and vertebra is delayed at E17.5

delayed endochondral bone ossification ( J:80670 )

delayed intramembranous bone ossification ( J:80670 )

• intramembranous bone formation is initiated but is either prematurely terminated or delayed at an early stage of osteoblast differentiation

vision/eye

eyelids open at birth ( J:80670 )

• delay in or incomplete closure of the eyelids

digestive/alimentary system

protruding tongue ( J:80670 )

limbs/digits/tail

bowed tibia ( J:80670 )

short limbs ( J:80670 )

liver/biliary system

abnormal liver morphology ( J:80670 )

• decrease in the percentage of CD19+ and B220+ B cells, GR1+ neutrophils and Mac-1+ cells in fetal liver

endocrine/exocrine glands

small thymus ( J:80670 )

• thymus is small and contains 50% fewer cells than in wild-type

growth/size/body

protruding tongue ( J:80670 )

short snout ( J:80670 )