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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
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 Background Strain C57BL/6J Donor Strain 129X1 x 129S1 via R1 (+Kitl-SlJ) ES cell line Generation N?+12p (07-NOV-04) Donating Investigator IMR Colony, The Jackson Laboratory Appearance
black
Related Genotype: a/aDescription
Mice homozygous for the Kdrtm1Jrt targeted mutation (formerly called Flk1) die at ~E8.5-E9.5 due to defects in hematopoietic and endothelial development. Embryos lack blood islands at E7.5 and fail to form organized blood vessels. There is severe reduction in hematopoietic progenitor cells.Development
This strain was developed in the lab of Dr. Janet Rossant at the University of Toronto. The insertion vector contains lacZ and neo.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (186 strains)
008685 FVB-Tg(tetO-Kdr*)4377.5Rwng/J
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
Kdrtm1Jrt/Kdrtm1Jrt
B6.129-Kdrtm1Jrt/J
- cardiovascular system phenotype
- abnormal dorsal aorta morphology (MGI Ref ID J:96124)
- at E8.5, dorsal aorta is absent
- absent organized vascular network (MGI Ref ID J:96124)
- at E8.5 vessels in the head as well as the dorsal aorta and vitelline artery are absent
- at E9.5 no blood vessels are seen
- embryogenesis phenotype
- abnormal mesoderm development (MGI Ref ID J:96124)
- at E7.5 the extraembryonic mesoderm consists of only a single cell layer
- absent blood islands (MGI Ref ID J:96124)
- at E7.5
- absent vitelline blood vessels (MGI Ref ID J:96124)
- at E9.5
- hematopoietic system phenotype
- impaired hematopoiesis (MGI Ref ID J:96124)
- the number of hematopoietic progenitors and the number of erythoid, granulocyte/macrophage and mixed colonies formed are severely reduced
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Kdrtm1Jrt/Kdr+
involves: 129S1/Sv * 129X1/SvJ
- normal phenotype
- no abnormal phenotype detected (MGI Ref ID J:26846)
Kdrtm1Jrt/Kdrtm1Jrt
involves: 129S1/Sv * 129X1/SvJ
- lethality-prenatal/perinatal
- embryonic lethality during organogenesis (MGI Ref ID J:26846)
- no embryos are recovered at E10.5 but are present at E9.5
- embryogenesis phenotype
- abnormal allantois morphology (MGI Ref ID J:125783)
- allantois explants fail to form any endothelial structures
- abnormal embryonic tissue morphology (MGI Ref ID J:26846)
- absent blood islands (MGI Ref ID J:26846)
- absent vitelline blood vessels (MGI Ref ID J:26846)
- at E8.5, yolk sac lack blood vessels and consist of a single layer of mesothelium lining the yolk sac endothelium
- decreased embryo size (MGI Ref ID J:26846)
- at E9.5
- cardiovascular system phenotype
- absent organized vascular network (MGI Ref ID J:26846)
- congestive heart failure (MGI Ref ID J:26846)
- embryos exhibit necrosis likely from cardiac failure
- hematopoietic system phenotype
- abnormal hematopoiesis (MGI Ref ID J:26846)
- expression of markers for hematopiesis could not be detected at E8.5
- at E8.5 only very rare committed hematopoietic cells could be identified by methylcellulose colony assay
- growth/size phenotype
- decreased embryo size (MGI Ref ID J:26846)
- at E9.5
- cellular phenotype
- necrosis (MGI Ref ID J:26846)
- embryos exhibit necrosis likely from cardiac failure
Kdrtm1Jrt/Kdrtm1Jrt
Background Not Specified
- cardiovascular system phenotype
- absent organized vascular network (MGI Ref ID J:95387)
- Kdr+ cells (lacZ expressing) reach the anterior portion portion of the embryo but no blood vessels develop
This mouse can be used to support research in many areas including:
Kdrtm1Jrt relatedDevelopmental Biology Research
Embryonic Lethality (Homozygous)
Internal/Organ Defects
hematopoietic defects
Lymphoid Tissue Defects
hematopoietic defects
Hematological Research
Hematopoietic Defects
Research Tools
lacZ Expression
Hematological Research
Cancer Research
Growth Factors/Receptors/Cytokines
Cardiovascular Research
Vascular Defects
Developmental Biology Research
Internal/Organ Defects
vasculature
Hematological Research
Hematopoietic Defects
Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Kdrtm1Jrt | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Janet Rossant | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | Flk1-; Flk1-lacZ neo-in; Flk1lacZ; Flk1lacZ; VEGFR-2-; VEGFR@lacZ; flk-1-; flk-1/lacZ; flk.lacZ; | ||
| Mutation Made By | Janet Rossant, The Hospital for Sick Children | ||
| Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| ES Cell Line Name | R1 | ||
| ES Cell Line Strain | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| Site of Expression | The vascular endothelial lineage. | ||
| Gene Symbol and Name | Kdr, kinase insert domain protein receptor | ||
| Chromosome | 5 | ||
| Gene Common Name(s) | CD309; FLK1; Flk-1; Flk1; MGC93590; VEGF receptor-2; VEGFR; VEGFR-2; VEGFR2; fetal liver kinase 1; vascular endothelial growth factor receptor- 2; | ||
| Molecular Note | Insertion of an in-frame lacZ gene and a floxed PGK-neomycin resistance cassette replaced the translated portion of the first coding exon and the proximal part of the next intron, and placed lacZ under the transcriptional control of the endogenous promoter. Neither RT-PCR using total RNA nor Western blot analysis using a carboxy terminal antibody detected gene expression in E8.5 homozygous mutant embryos. [MGI Ref ID J:26846] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Kdrtm1Jrt, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Shalaby F; Rossant J; Yamaguchi TP; Gertsenstein M; Wu XF; Breitman ML; Schuh AC. 1995. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376(6535):62-6. [PubMed: 7596435] [MGI Ref ID J:26846]
Additional References
Brennan J; Karl J; Capel B. 2002. Divergent Vascular Mechanisms Downstream of Sry Establish the Arterial System in the XY Gonad. Dev Biol 244(2):418-28. [PubMed: 11944948] [MGI Ref ID J:76133]
Welsh IC; O'Brien TP. 2000. Loss of late primitive streak mesoderm and interruption of left-right morphogenesis in the Ednrb(s-1Acrg) mutant mouse. Dev Biol 225(1):151-68. [PubMed: 10964471] [MGI Ref ID J:64329]
Kdrtm1Jrt relatedAhlbrecht K; Schmitz J; Seay U; Schwarz C; Mittnacht-Kraus R; Gaumann A; Haberberger RV; Herold S; Breier G; Grimminger F; Seeger W; Voswinckel R. 2008. Spatiotemporal expression of flk-1 in pulmonary epithelial cells during lung development. Am J Respir Cell Mol Biol 39(2):163-70. [PubMed: 18323533] [MGI Ref ID J:151060]
Baumer S; Keller L; Holtmann A; Funke R; August B; Gamp A; Wolburg H; Wolburg-Buchholz K; Deutsch U; Vestweber D. 2006. Vascular endothelial cell-specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development. Blood 107(12):4754-62. [PubMed: 16514057] [MGI Ref ID J:125783]
Carpenter B; Lin Y; Stoll S; Raffai RL; McCuskey R; Wang R. 2005. VEGF is crucial for the hepatic vascular development required for lipoprotein uptake. Development 132(14):3293-303. [PubMed: 15944181] [MGI Ref ID J:100427]
Chen TH; Chang TC; Kang JO; Choudhary B; Makita T; Tran CM; Burch JB; Eid H; Sucov HM. 2002. Epicardial induction of fetal cardiomyocyte proliferation via a retinoic acid-inducible trophic factor. Dev Biol 250(1):198-207. [PubMed: 12297106] [MGI Ref ID J:107701]
De Langhe SP; Carraro G; Tefft D; Li C; Xu X; Chai Y; Minoo P; Hajihosseini MK; Drouin J; Kaartinen V; Bellusci S. 2008. Formation and Differentiation of Multiple Mesenchymal Lineages during Lung Development Is Regulated by beta-catenin Signaling. PLoS ONE 3(1):e1516. [PubMed: 18231602] [MGI Ref ID J:131535]
Duan LJ; Nagy A; Fong GH. 2003. Gastrulation and angiogenesis, not endothelial specification, is sensitive to partial deficiency in vascular endothelial growth factor-a in mice. Biol Reprod 69(6):1852-8. [PubMed: 12890722] [MGI Ref ID J:86673]
Fuster MM; Wang L; Castagnola J; Sikora L; Reddi K; Lee PH; Radek KA; Schuksz M; Bishop JR; Gallo RL; Sriramarao P; Esko JD. 2007. Genetic alteration of endothelial heparan sulfate selectively inhibits tumor angiogenesis. J Cell Biol 177(3):539-49. [PubMed: 17470635] [MGI Ref ID J:134728]
Hart A; Melet F; Grossfeld P; Chien K; Jones C; Tunnacliffe A; Favier R; Bernstein A. 2000. Fli-1 is required for murine vascular and megakaryocytic development and is hemizygously deleted in patients with thrombocytopenia Immunity 13(2):167-77. [PubMed: 10981960] [MGI Ref ID J:64178]
Hiratsuka S; Kataoka Y; Nakao K; Nakamura K; Morikawa S; Tanaka S; Katsuki M; Maru Y; Shibuya M. 2005. Vascular endothelial growth factor A (VEGF-A) is involved in guidance of VEGF receptor-positive cells to the anterior portion of early embryos. Mol Cell Biol 25(1):355-63. [PubMed: 15601856] [MGI Ref ID J:95386]
Hiratsuka S; Nakao K; Nakamura K; Katsuki M; Maru Y; Shibuya M. 2005. Membrane fixation of vascular endothelial growth factor receptor 1 ligand-binding domain is important for vasculogenesis and angiogenesis in mice. Mol Cell Biol 25(1):346-54. [PubMed: 15601855] [MGI Ref ID J:95387]
Hirota Y; Tranguch S; Daikoku T; Hasegawa A; Osuga Y; Taketani Y; Dey SK. 2008. Deficiency of immunophilin FKBP52 promotes endometriosis. Am J Pathol 173(6):1747-57. [PubMed: 18988805] [MGI Ref ID J:141411]
Hong KH; Seki T; Oh SP. 2007. Activin receptor-like kinase 1 is essential for placental vascular development in mice. Lab Invest 87(7):670-9. [PubMed: 17530030] [MGI Ref ID J:122868]
Inman KE; Downs KM. 2006. Brachyury is required for elongation and vasculogenesis in the murine allantois. Development 133(15):2947-59. [PubMed: 16835439] [MGI Ref ID J:119027]
Jacquemin P; Yoshitomi H; Kashima Y; Rousseau GG; Lemaigre FP; Zaret KS. 2006. An endothelial-mesenchymal relay pathway regulates early phases of pancreas development. Dev Biol 290(1):189-99. [PubMed: 16386727] [MGI Ref ID J:104894]
Li B; Vincent A; Cates J; Brantley-Sieders DM; Polk DB; Young PP. 2009. Low levels of tumor necrosis factor alpha increase tumor growth by inducing an endothelial phenotype of monocytes recruited to the tumor site. Cancer Res 69(1):338-48. [PubMed: 19118019] [MGI Ref ID J:143025]
Mallory BP; Mead TJ; Wiginton DA; Kulkarni RM; Greenberg JM; Akeson AL. 2006. Lymphangiogenesis in the developing lung promoted by VEGF-A. Microvasc Res 72(1-2):62-73. [PubMed: 16806288] [MGI Ref ID J:129289]
Manuylov NL; Smagulova FO; Leach L; Tevosian SG. 2008. Ovarian development in mice requires the GATA4-FOG2 transcription complex. Development 135(22):3731-43. [PubMed: 18927154] [MGI Ref ID J:143586]
Matsumoto H; Ma WG; Daikoku T; Zhao X; Paria BC; Das SK; Trzaskos JM; Dey SK. 2002. Cyclooxygenase-2 differentially directs uterine angiogenesis during implantation in mice. J Biol Chem 277(32):29260-7. [PubMed: 12034746] [MGI Ref ID J:78279]
Matsumoto K; Yoshitomi H; Rossant J; Zaret KS. 2001. Liver organogenesis promoted by endothelial cells prior to vascular function. Science 294(5542):559-63. [PubMed: 11577199] [MGI Ref ID J:72168]
Murakami M; Zheng Y; Hirashima M; Suda T; Morita Y; Ooehara J; Ema H; Fong GH; Shibuya M. 2008. VEGFR1 tyrosine kinase signaling promotes lymphangiogenesis as well as angiogenesis indirectly via macrophage recruitment. Arterioscler Thromb Vasc Biol 28(4):658-64. [PubMed: 18174461] [MGI Ref ID J:149043]
Nakajima M; Yuasa S; Ueno M; Takakura N; Koseki H; Shirasawa T. 2003. Abnormal blood vessel development in mice lacking presenilin-1. Mech Dev 120(6):657-67. [PubMed: 12834865] [MGI Ref ID J:84418]
Petrova TV; Karpanen T; Norrmen C; Mellor R; Tamakoshi T; Finegold D; Ferrell R; Kerjaschki D; Mortimer P; Yla-Herttuala S; Miura N; Alitalo K. 2004. Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis. Nat Med 10(9):974-981. [PubMed: 15322537] [MGI Ref ID J:92818]
Sakurai Y; Ohgimoto K; Kataoka Y; Yoshida N; Shibuya M. 2005. Essential role of Flk-1 (VEGF receptor 2) tyrosine residue 1173 in vasculogenesis in mice. Proc Natl Acad Sci U S A 102(4):1076-81. [PubMed: 15644447] [MGI Ref ID J:96124]
Seki T; Hong KH; Oh SP. 2006. Nonoverlapping expression patterns of ALK1 and ALK5 reveal distinct roles of each receptor in vascular development. Lab Invest 86(2):116-29. [PubMed: 16344855] [MGI Ref ID J:104918]
Seki T; Yun J; Oh SP. 2003. Arterial endothelium-specific activin receptor-like kinase 1 expression suggests its role in arterialization and vascular remodeling. Circ Res 93(7):682-9. [PubMed: 12970115] [MGI Ref ID J:85877]
Shalaby F; Ho J; Stanford WL; Fischer KD; Schuh AC; Schwartz L ; Bernstein A ; Rossant J. 1997. A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell 89(6):981-90. [PubMed: 9200616] [MGI Ref ID J:41435]
Shi Y; Reitmaier B; Regenbogen J; Slowey RM; Opalenik SR; Wolf E; Goppelt A; Davidson JM. 2005. CARP, a cardiac ankyrin repeat protein, is up-regulated during wound healing and induces angiogenesis in experimental granulation tissue. Am J Pathol 166(1):303-12. [PubMed: 15632022] [MGI Ref ID J:95323]
Tang T; Shi Y; Opalenik SR; Brantley-Sieders DM; Chen J; Davidson JM; Brandt SJ. 2006. Expression of the TAL1/SCL transcription factor in physiological and pathological vascular processes. J Pathol 210(1):121-9. [PubMed: 16841371] [MGI Ref ID J:112352]
Wada T; Haigh JJ; Ema M; Hitoshi S; Chaddah R; Rossant J; Nagy A; van der Kooy D. 2006. Vascular endothelial growth factor directly inhibits primitive neural stem cell survival but promotes definitive neural stem cell survival. J Neurosci 26(25):6803-12. [PubMed: 16793887] [MGI Ref ID J:109983]
Wang H; Xie H; Sun X; Tranguch S; Zhang H; Jia X; Wang D; Das SK; Desvergne B; Wahli W; Dubois RN; Dey SK. 2007. Stage-specific Integration of Maternal and Embryonic Peroxisome Proliferator-activated Receptor {delta} Signaling Is Critical to Pregnancy Success. J Biol Chem 282(52):37770-37782. [PubMed: 17965409] [MGI Ref ID J:128959]
Weaver M; Batts L; Hogan BL. 2003. Tissue interactions pattern the mesenchyme of the embryonic mouse lung. Dev Biol 258(1):169-84. [PubMed: 12781691] [MGI Ref ID J:83697]
Wirzenius M; Tammela T; Uutela M; He Y; Odorisio T; Zambruno G; Nagy JA; Dvorak HF; Yla-Herttuala S; Shibuya M; Alitalo K. 2007. Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting. J Exp Med 204(6):1431-40. [PubMed: 17535974] [MGI Ref ID J:125859]
Yoshitomi H; Zaret KS. 2004. Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a. Development 131(4):807-17. [PubMed: 14736742] [MGI Ref ID J:87724]
del Moral PM; De Langhe SP; Sala FG; Veltmaat JM; Tefft D; Wang K; Warburton D; Bellusci S. 2006. Differential role of FGF9 on epithelium and mesenchyme in mouse embryonic lung. Dev Biol 293(1):77-89. [PubMed: 16494859] [MGI Ref ID J:108388]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Additional Supply Details
| Pricing for International shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Additional Supply Details
|
|
|
Supply Details
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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.Ordering and Purchasing Information
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JAX® Mice, Products & Services Conditions of Use
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.No Warranty
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