Phenotypes associated with this allele

• Allele Symbol: Sf3b1⁺
• Allele Name: wild type
• Allele ID: MGI:2436554
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Sf3b1^tm1Hko/Sf3b1^+	B6.Cg-Sf3b1^tm1Hko	MGI:3574649
ht2	Sf3b1^tm1Hko/Sf3b1^+	Not Specified	MGI:7279138
cn3	Sf3b1^tm1.1Mdf/Sf3b1^+ Tg(Mx1-cre)1Cgn/?	involves: 129S4/SvJae * C57BL/6 * CBA/J	MGI:5823482
cn4	Sf3b1^tm1.1Mdf/Sf3b1^+ Tet2^tm1.1Iaai/Tet2^tm1.1Iaai Tg(Mx1-cre)1Cgn/?	involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * CBA/J	MGI:5823559
cx5	Kmt2a^tm1Tok/Kmt2a^+ Sf3b1^tm1Hko/Sf3b1^+	involves: C57BL/6	MGI:3574650
cx6	Pcgf2^tm1Hko/Pcgf2^+ Sf3b1^tm1Hko/Sf3b1^+	involves: C57BL/6	MGI:3574652

Genotype
MGI:3574649

ht1

• Allelic Composition: Sf3b1^tm1Hko/Sf3b1⁺
• Genetic Background: B6.Cg-Sf3b1^tm1Hko

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

skeleton

thoracic vertebral transformation ( J:96358 )

• 29% of heterozygotes had a prominent spinous process, characteristic for the second thoracic vertebra (T2), incorrectly associated with T1, suggesting a T1 to T2 transformation

• 6% of heterozygotes had only 12 ribs, indicating T13 to L1 transformation

cervical vertebral transformation ( J:96358 )

• 27% of heterozygotes had the seventh cervical vertebra (C7) with incomplete ectopic ribs, either unilaterally or bilaterally fused with the first thoracic rib, indicating transformations of C7 toward the first thoracic vertebra (T1)

lumbar vertebral transformation ( J:96358 )

• 88% had five lumbar vertebrae, indicating an L6 to S1 transformation

Genotype
MGI:7279138

ht2

• Allelic Composition: Sf3b1^tm1Hko/Sf3b1⁺
• Genetic Background: Not Specified

behavior/neurological

hypoactivity ( J:324276 )

• some mice start to show a decline in overall activity after 12 months of age, showing reduced movements and difficulty walking

hematopoietic system

extramedullary hematopoiesis ( J:324276 )

• extramedullary hematopoiesis in the spleen, with hematopoietic elements, increased megakaryocytes with hyperchromatic nuclei, increased hemosiderin deposits and signs of fibrosis

• however, no hepatomegaly or microscopic abnormalities in the liver are seen

macrocytic anemia ( J:324276 )

abnormal bone marrow cell morphology/development ( J:324276 )

• bone marrow cells show dyserythropoietic features including nuclear budding or nuclear irregularity

• occasionally ring sideroblasts are seen in the bone marrow

decreased erythrocyte cell number ( J:324276 )

• mice tend to have lower red blood cell levels at 6, 8, 9, 11, and 12 months but statistically significant difference is seen at 11 and 12 months

decreased hemoglobin content ( J:324276 )

• mice tend to have lower hemoglobin levels at 6, 8, 9, 11, and 12 months but statistically significant difference is seen at 11 months

increased mean corpuscular volume ( J:324276 )

• mice exhibit higher mean corpuscular volume at 6 to 12 months of age, indicating macrocytic anemia

thrombocytosis ( J:324276 )

• platelet counts increase at 6 months until 12 months of age with a significant difference at 10 months

increased spleen red pulp amount ( J:324276 )

• spleen shows expansion of the red pulp

immune system

increased spleen red pulp amount ( J:324276 )

• spleen shows expansion of the red pulp

reproductive system

reduced fertility ( J:324276 )

• fertility of breeding pairs drops dramatically after 6 months of age and no progeny is produced by mice of this age or older

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myelodysplastic syndrome		DOID:0050908	OMIM:614286	J:324276

Genotype
MGI:5823482

cn3

• Allelic Composition: Sf3b1^tm1.1Mdf/Sf3b1⁺; Tg(Mx1-cre)1Cgn/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA/J

hematopoietic system

abnormal erythropoiesis ( J:234976 )

• block in erythroblast development resulting in an increase in cells at development stage R2 and a decrease in R4 cell population in spleen and bone marrow 64 weeks post-piPC

abnormal myelopoiesis ( J:234976 )

• transplantation of bone marrow from mutants into lethally irradiated CD45.1 recipient mice that were treated with pIPC results in lower peripheral blood chimerism

• chimerism is lower in LT-HSC to committed myeloid progenitors

• increase in long term repopulating hematopoietic stem cells (LT-HSC) in bone marrow 45 and 64 weeks post-piPC treatment, however, repopulating ability is decrease

• decrease in percentage of granulocyte/monocyte progenitors

hypochromic macrocytic anemia ( J:234976 )

• progressive macrocytic anemia develops following pIPC injection

• anemia is present 4-8 weeks post-injection and is severe by 20 weeks

impaired hematopoiesis ( J:234976 )

• lower percentage of hematopoietic and stem progenitor cells in G1 and a higher percentage in G0 in vitro (24 weeks post-pIPC) as compared to control

decreased granulocyte monocyte progenitor cell number ( J:234976 )

• decrease in percentage of granulocyte/monocyte progenitors in aged mice

abnormal erythroid progenitor cell morphology ( J:234976 )

• increase in erythroid precursors in spleens is observed at 64 weeks post-pIPC

• erythroid dysplasia in spleens is observed at 47 weeks post-pIPC

decreased erythrocyte cell number ( J:234976 )

• total red blood cell number is decreased beginning at 20 weeks post-pIPC injection

• no differences in total white blood cell count, mature white blood cell lineages or platelet counts

increased mean corpuscular volume ( J:234976 )

• beginning at 20 weeks post-pIPC injectio

macrocytosis ( J:234976 )

• macrocytosis is apparent at 20 weeks post-pIPC injection

increased hematopoietic stem cell number ( J:234976 )

• increase in long term repopulating hematopoietic stem cells (LT-HSC) in bone marrow 64 weeks post-piPC treatment, however, repopulating ability is decreased

• no differences in short-term hematopoietic stem cells, multi potent progenitors, common myeloid progenitors, megakaryocytic/erythroid progenitors or colony forming units at 64 weeks post-pIPC

• increase in multi-potent progenitors (MPP) in bone marrow at 12 weeks, but not 45 weeks post-piPC treatment

homeostasis/metabolism

increased circulating erythropoietin level ( J:234976 )

• plasma erythropoietin levels are increased and persist for longer than 60 weeks post-pIPC as compared to wild-type

immune system

abnormal myelopoiesis ( J:234976 )

• transplantation of bone marrow from mutants into lethally irradiated CD45.1 recipient mice that were treated with pIPC results in lower peripheral blood chimerism

• chimerism is lower in LT-HSC to committed myeloid progenitors

• increase in long term repopulating hematopoietic stem cells (LT-HSC) in bone marrow 45 and 64 weeks post-piPC treatment, however, repopulating ability is decrease

• decrease in percentage of granulocyte/monocyte progenitors

mortality/aging

premature death ( J:234976 )

• 2 mice (18%) die by 64 weeks post piPC no wild-type mice die during this time

Genotype
MGI:5823559

cn4

• Allelic Composition: Sf3b1^tm1.1Mdf/Sf3b1⁺; Tet2^tm1.1Iaai/Tet2^tm1.1Iaai; Tg(Mx1-cre)1Cgn/?
• Genetic Background: involves: 129S/SvEv * 129S4/SvJae * C57BL/6 * CBA/J

hematopoietic system

enlarged spleen ( J:234976 )

• post-piPC treatment

abnormal erythropoiesis ( J:234976 )

• block in erythroblast development results in an increase in cells at development stage R2 and a decrease in R4 population in spleen by 12 weeks post-piPC

abnormal myelopoiesis ( J:234976 )

• transplantation of bone marrow from mutants into lethally irradiated CD45.1 recipient mice that were treated with pIPC results in increasing (46.5% to 90%) donor chimerism beginning at 16 weeks post transplantation as compared to mice carrying only the Sf3b1^tm1.1Mdf allele and wild-type

hypochromic macrocytic anemia ( J:234976 )

• progressive macrocytic anemia 45 weeks post pIPC treatment

abnormal megakaryocyte morphology ( J:234976 )

• spleens contain dysplastic megakaryocytes 45 weeks post-piPC treatment

abnormal erythroid progenitor cell morphology ( J:234976 )

• spleens contain dysplastic erythroid progenitors 45 weeks post-piPC treatment

increased mean corpuscular volume ( J:234976 )

• observed at 45 weeks post-pIPC injection

• phenotype is increased in severity as compared to mice carrying only the Sf3b1^tm1.1Mdf allele

macrocytosis ( J:234976 )

• post-pIPC treatment

increased granulocyte number ( J:234976 )

• increased percentage of granulocytes in peripheral blood and bone marrow at 45 weeks post-pIPC

decreased B cell number ( J:234976 )

• decrease in percentage of B cells in the spleen and bone marrow 45 weeks post-pIPC

increased hematopoietic stem cell number ( J:234976 )

• increase in long term repopulating hematopoietic stem cells (LT-HSC) at 12 and 45 weeks as compared to wild-type

• increase in multi-potent progenitors (MPP) in bone marrow 12 weeks post-piPC treatment

immune system

enlarged spleen ( J:234976 )

• post-piPC treatment

abnormal myelopoiesis ( J:234976 )

• transplantation of bone marrow from mutants into lethally irradiated CD45.1 recipient mice that were treated with pIPC results in increasing (46.5% to 90%) donor chimerism beginning at 16 weeks post transplantation as compared to mice carrying only the Sf3b1^tm1.1Mdf allele and wild-type

increased granulocyte number ( J:234976 )

• increased percentage of granulocytes in peripheral blood and bone marrow at 45 weeks post-pIPC

decreased B cell number ( J:234976 )

• decrease in percentage of B cells in the spleen and bone marrow 45 weeks post-pIPC

growth/size/body

enlarged spleen ( J:234976 )

• post-piPC treatment

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myelodysplastic syndrome		DOID:0050908	OMIM:614286	J:234976

Genotype
MGI:3574650

cx5

• Allelic Composition: Kmt2a^tm1Tok/Kmt2a⁺; Sf3b1^tm1Hko/Sf3b1⁺
• Genetic Background: involves: C57BL/6

skeleton

skeleton phenotype ( J:96358 )

N • posterior vertebral transformations at the cervico-thoracic transitional zone caused by the Sf3b1 mutation were completely restored in double heterozygous mice

Genotype
MGI:3574652

cx6

• Allelic Composition: Pcgf2^tm1Hko/Pcgf2⁺; Sf3b1^tm1Hko/Sf3b1⁺
• Genetic Background: involves: C57BL/6

skeleton

abnormal sternocostal joint morphology ( J:96358 )

• the detachment of the ribs of T7 from the sternum, representing an anterior shift of the sternum of one segment width

vertebral transformation ( J:96358 )

thoracic vertebral transformation ( J:96358 )

• 75% exhibit T1 to T2 transformation

• 50% exhibit T13 to L1 transformation

cervical vertebral transformation ( J:96358 )

• 45% exhibit C7 to T1 transformation, and showed ectopic ribs associated with C7 mimicking perfect ribs and forming joints with the anteriorly shifted sternum

lumbar vertebral transformation ( J:96358 )

• 100% exhibit an L6 to S1 transformation

abnormal sternum ossification ( J:96358 )

• the formation of an additional ossification center in the sternum