Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation ?+N1p (13-MAR-05) Generation Definitions   Donating Investigator Dr. Michael L. Mucenski,   Children's Hospital Research Fdn

Description
Homozygous null mice have an embryonic lethal phenotype, failing to develop past embryonic days 15.5. At embryonic day 13, homozygotes are normal in size and morphology, but have 10 fold lower hematocrit levels, due to anemia caused by diminished fetal hepatic erthropoiesis. In vitro examination of cells from the para-aortic, splanchnopleural (P-Sp) and aorta-gonad-mesonephros regions reveals defective hematopoiesis. Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This mutant mouse strain may be useful in studies of fetal definitive hematopoiesis.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 6. The construct was electroporated into 129S2/SvPas derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for at least 6 generations.

Control Information

	Control
	See control note:	Wildtype mice from the colony or C57BL/6J mice (Stock No. 000664) may be used as controls.
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Myb^tm1Ssp/Myb^tm1Ssp

        either: (involves: 129P2/OlaHsd * C57BL/6J) or (involves: 129P2/OlaHsd * CD-1)

• mortality/aging
• complete lethality throughout fetal growth and development
  • homozygotes usually die at E15, presumably of anoxia   (MGI Ref ID J:43747)
• hematopoietic system phenotype
• abnormal erythropoiesis
  • at E15, peripheral blood smears of homozygous mutant fetuses display predominantly large, nucleated yolk-sac derived erythrocytes, with only a few (~20%) non-nucleated erythrocytes typical of liver-derived erythropoiesis, indicating a defect in adult-type erythropoiesis   (MGI Ref ID J:43747)
  • in contrast, embryonic erytrhopoiesis appears largely unaffected   (MGI Ref ID J:43747)
• • anemia
    • all homozygous mutant fetuses become severely anemic by E15   (MGI Ref ID J:43747)
  • decreased erythroid progenitor cell number
    • only rare, diffusely distributed erythroid cells are identifiable in mutant liver touch preparations at E15   (MGI Ref ID J:43747)
    • however, no significant differences in megalokaryocyte number or morphology are observed relative to control littermates   (MGI Ref ID J:43747)
  • decreased hematocrit
    • whereas hematocrits of wild-type and heterozygous fetuses remain in the 30%-40% range between E12 and E15, those of homozygous mutant fetuses drop significantly to values of ~5% between E13 and E15   (MGI Ref ID J:43747)
    • by E15, homozygous mutant fetuses show a 10-fold reduction in hematocrit levels relative to wild-type or heterozygous controls   (MGI Ref ID J:43747)
  • increased nucleated erythrocyte cell number
    • at E13-E15, homozygous mutant embryos exhibit a high % of nucleated RBCs (~80%) relative to wild-type and heterozygous embryos (<5%), indicating persistence of yolk-sac derived primitive erythrocytes   (MGI Ref ID J:43747)
• decreased common myeloid progenitor cell number
  • only rare, immature monocytoid cells are identifiable in mutant liver touch preparations at E15   (MGI Ref ID J:43747)
• decreased hematopoietic stem cell number
  • at least 88% less CFU-GM progenitor cells are identifiable in mutant livers at E14 and E15   (MGI Ref ID J:43747)
• liver/biliary system phenotype
• abnormal liver sinusoid morphology
  • no erythropoietic islands are detectable in mutant liver sinusoids at E15   (MGI Ref ID J:43747)
• small liver
  • at E14 and E15, mutant livers are grossly smaller than normal   (MGI Ref ID J:43747)
• cardiovascular system phenotype
• abnormal liver sinusoid morphology
  • no erythropoietic islands are detectable in mutant liver sinusoids at E15   (MGI Ref ID J:43747)
• integument phenotype
• pallor
  • at E15, homozygous mutant fetuses are grossly normal in size and shape but appear significantly pale   (MGI Ref ID J:43747)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Myb^tm1Ssp related

Developmental Biology Research
Embryonic Lethality (Homozygous)

Hematological Research
Hematopoietic Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Mybtm1Ssp
Allele Name		targeted mutation 1, S Steven Potter
Allele Type		Targeted (knock-out)
Mutation Made By		Dr. Michael Mucenski,   Children's Hospital Research Fdn
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Myb, myeloblastosis oncogene
Chromosome		10
Gene Common Name(s)		AI550390; Cmyb; M16449; c-myb; c-myb_CDS; efg; expressed sequence AI550390; expressed sequence M16449;
Molecular Note		The endogenous locus was disrupted by the insertion of a neomycin selection cassette into exon 6. [MGI Ref ID J:43747]

Genotyping

Genotyping Information

Genotyping Protocols

Myb^tm1Ssp, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Mucenski ML; McLain K; Kier AB; Swerdlow SH; Schreiner CM; Miller TA ; Pietryga DW ; Scott WJ Jr ; Potter SS. 1991. A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis. Cell 65(4):677-89. [PubMed: 1709592]  [MGI Ref ID J:43747]

Additional References

Mukouyama Ys; Chiba N; Mucenski ML; Satake M; Miyajima A; Hara T; Watanabe T. 1999. Hematopoietic cells in cultures of the murine embryonic aorta-gonad-mesonephros region are induced by c-Myb. Curr Biol 9(15):833-6. [PubMed: 10469571]  [MGI Ref ID J:56652]

Sumner R; Crawford A; Mucenski M; Frampton J. 2000. Initiation of adult myelopoiesis can occur in the absence of c-Myb whereas subsequent development is strictly dependent on the transcription factor. Oncogene 19(30):3335-42. [PubMed: 10918590]  [MGI Ref ID J:63787]

Myb^tm1Ssp related

Allen RD 3rd; Bender TP; Siu G. 1999. c-Myb is essential for early T cell development. Genes Dev 13(9):1073-8. [PubMed: 10323859]  [MGI Ref ID J:55049]

Emambokus N; Vegiopoulos A; Harman B; Jenkinson E; Anderson G; Frampton J. 2003. Progression through key stages of haemopoiesis is dependent on distinct threshold levels of c-Myb. EMBO J 22(17):4478-88. [PubMed: 12941699]  [MGI Ref ID J:85344]

Kasper LH; Boussouar F; Ney PA; Jackson CW; Rehg J; van Deursen JM; Brindle PK. 2002. A transcription-factor-binding surface of coactivator p300 is required for haematopoiesis. Nature 419(6908):738-43. [PubMed: 12384703]  [MGI Ref ID J:98329]

Kopecki Z; Luchetti MM; Adams DH; Strudwick X; Mantamadiotis T; Stoppacciaro A; Gabrielli A; Ramsay RG; Cowin AJ. 2007. Collagen loss and impaired wound healing is associated with c-Myb deficiency. J Pathol 211(3):351-61. [PubMed: 17152050]  [MGI Ref ID J:118283]

Mizuochi C; Fraser ST; Biasch K; Horio Y; Kikushige Y; Tani K; Akashi K; Tavian M; Sugiyama D. 2012. Intra-aortic clusters undergo endothelial to hematopoietic phenotypic transition during early embryogenesis. PLoS One 7(4):e35763. [PubMed: 22558218]  [MGI Ref ID J:187282]

Mukouyama Ys; Chiba N; Mucenski ML; Satake M; Miyajima A; Hara T; Watanabe T. 1999. Hematopoietic cells in cultures of the murine embryonic aorta-gonad-mesonephros region are induced by c-Myb. Curr Biol 9(15):833-6. [PubMed: 10469571]  [MGI Ref ID J:56652]

Okada H; Watanabe T; Niki M; Takano H; Chiba N; Yanai N; Tani K; Hibino H; Asano S; Mucenski ML; Ito Y; Noda T; Satake M. 1998. AML1(-/-) embryos do not express certain hematopoiesis-related gene transcripts including those of the PU.1 gene. Oncogene 17(18):2287-93. [PubMed: 9811459]  [MGI Ref ID J:50937]

Ramsay RG; Micallef S; Lightowler S; Mucenski ML; Mantamadiotis T; Bertoncello I. 2004. c-myb Heterozygous mice are hypersensitive to 5-fluorouracil and ionizing radiation. Mol Cancer Res 2(6):354-61. [PubMed: 15235111]  [MGI Ref ID J:91223]

Sicurella C; Freeman R; Micallef S; Mucenski ML; Bertoncello I; Ramsay RG. 2001. Defective stem cell factor expression in c-myb null fetal liver stroma. Blood Cells Mol Dis 27(2):470-8. [PubMed: 11259170]  [MGI Ref ID J:108609]

Sumner R; Crawford A; Mucenski M; Frampton J. 2000. Initiation of adult myelopoiesis can occur in the absence of c-Myb whereas subsequent development is strictly dependent on the transcription factor. Oncogene 19(30):3335-42. [PubMed: 10918590]  [MGI Ref ID J:63787]

Takakura N; Watanabe T; Suenobu S; Yamada Y; Noda T; Ito Y; Satake M; Suda T. 2000. A role for hematopoietic stem cells in promoting angiogenesis Cell 102(2):199-209. [PubMed: 10943840]  [MGI Ref ID J:63424]

Tober J; McGrath KE; Palis J. 2008. Primitive erythropoiesis and megakaryopoiesis in the yolk sac are independent of c-myb. Blood 111(5):2636-9. [PubMed: 18174377]  [MGI Ref ID J:131538]

Vegiopoulos A; Garcia P; Emambokus N; Frampton J. 2006. Coordination of erythropoiesis by the transcription factor c-Myb. Blood 107(12):4703-10. [PubMed: 16484593]  [MGI Ref ID J:132864]

Yokomizo T; Takahashi S; Mochizuki N; Kuroha T; Ema M; Wakamatsu A; Shimizu R; Ohneda O; Osato M; Okada H; Komori T; Ogawa M; Nishikawa S; Ito Y; Yamamoto M. 2007. Characterization of GATA-1(+) hemangioblastic cells in the mouse embryo. EMBO J 26(1):184-96. [PubMed: 17159898]  [MGI Ref ID J:117242]

Zorbas M; Sicurella C; Bertoncello I; Venter D; Ellis S; Mucenski ML; Ramsay RG. 1999. c-Myb is critical for murine colon development. Oncogene 18(42):5821-30. [PubMed: 10523863]  [MGI Ref ID J:58207]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	This strain must be maintained using heterozygotes due to homozygous embryonic lethal phenotype.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	See control note:	Wildtype mice from the colony or C57BL/6J mice (Stock No. 000664) may be used as controls.
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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