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-S3 (+Kitl-SlJ) ES cell line   Donating Investigator IMR Colony,   The Jackson Laboratory

Appearance
black
Related Genotype: a/a

Description
In these Notch1 deficient mice, somitogenesis is disturbed and there is a probable defect in chorio-allantoic connection. Homozygotes die at embryonic day 9.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
The mutant was generated by deleting a large portion of the Notch1 gene using a positive/negative targeting vector. These mice have been backcrossed to C57BL/6J mice (Stock No. 000664) for at least 10 generations.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Notch1^tm1Con allele

002445

STOCK Notch1tm1Con/J

View Strains carrying   Notch1^tm1Con     (1 strain)

Strains carrying other alleles of Notch1

007181	B6.129X1-Notch1tm2Rko/GridJ
003332	C57BL/6-Tg(LckNotch1)9Erob/J
008159	STOCK Gt(ROSA)26Sortm1(Notch1)Dam/J
006951	STOCK Notch1tm2Rko/GridJ
006953	STOCK Notch1tm3(cre)Rko/J

View Strains carrying other alleles of Notch1     (5 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Aortic Valve Disease 1; AOVD1   (NOTCH1)

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.

Notch1^tm1Con/Notch1^tm1Con

        either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6) or (involves: 129S1/Sv * 129X1/SvJ * CD-1)

• mortality/aging
• complete embryonic lethality during organogenesis
  • most mutants are dead at E10 and all die by E11   (MGI Ref ID J:25248)
• embryogenesis phenotype
• abnormal rostral-caudal axis patterning
  • show a deficit in posterior development at E9   (MGI Ref ID J:25248)
• abnormal somite development   (MGI Ref ID J:62882)
  • mutants exhibit a lack of coordination in segmentation of the somites, leading to variable somite size and misalignment of the somites across the midline of the embryo   (MGI Ref ID J:25248)
  • transition from presomitic mesoderm to the somite is disordered   (MGI Ref ID J:25248)
  • the most recently formed somites are not as tightly packed as those of wild-type and the epithelialization sometimes appears incomplete   (MGI Ref ID J:25248)
• • abnormal left-right axis symmetry of the somites
    • lack of coordination across the midline in the segmentation of somites, where segmentation is sometimes present on one side but not the other   (MGI Ref ID J:25248)
  • abnormal somite size
    • variable somite size   (MGI Ref ID J:25248)
  • delayed somite formation
    • mutants exhibit a delay in segmentation of the somites   (MGI Ref ID J:25248)
• decreased embryo size
  • embryos are smaller at E9   (MGI Ref ID J:25248)
• embryonic growth arrest   (MGI Ref ID J:62882)
  • growth arrest at the 14 somite stage   (MGI Ref ID J:25248)
• kinked neural tube
  • neural tube kinks are seen extending posterior to the forelimb   (MGI Ref ID J:62882)
• notochord degeneration
  • the notochord degenerates after growth arrest   (MGI Ref ID J:25248)
• growth/size phenotype
• decreased embryo size
  • embryos are smaller at E9   (MGI Ref ID J:25248)
• cardiovascular system phenotype
• distended pericardium   (MGI Ref ID J:62882)
  • distended pericardia at E9   (MGI Ref ID J:25248)
• cellular phenotype
• abnormal cell death
  • an increase in cell death is seen in embryos after they arrest   (MGI Ref ID J:25248)
• nervous system phenotype
• kinked neural tube
  • neural tube kinks are seen extending posterior to the forelimb   (MGI Ref ID J:62882)

Notch1^tm1Con/Notch1^tm1Con

        involves: 129S1/Sv * 129X1/SvJ

• cardiovascular system phenotype
• abnormal myocardium layer morphology
  • the endocardium does not surround the myocardium, which shows irregular thickness   (MGI Ref ID J:119151)
• • disorganized myocardium
    • less-structured myocardium   (MGI Ref ID J:119151)
  • trabecula carnea hypoplasia   (MGI Ref ID J:119151)
• muscle phenotype
• trabecula carnea hypoplasia   (MGI Ref ID J:119151)

View Research Applications

Research Applications

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

Notch1^tm1Con related

Developmental Biology Research
Embryonic Lethality (Homozygous)

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Notch1tm1Con
Allele Name		targeted mutation 1, Ronald L Conlon
Allele Type		Targeted (knock-out)
Common Name(s)		N1delta1; Notch1-; Notch1tm1Con/J; Notch-; Notchdelta1;
Mutation Made By		Dr. Ronald Conlon,   Case Western Reserve Univ, School of Med
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<+>
Gene Symbol and Name		Notch1, notch 1
Chromosome		2
Gene Common Name(s)		9930111A19Rik; Mis6; Motch A; N1; NOTCH; RIKEN cDNA 9930111A19 gene; TAN1; Tan1; hN1; lin-12; translocation-associated Notch;
Molecular Note		Deletion of sequences encoding the EGF repeats 28 to 36, three Notch repeats, the transmembrane domain and CDC10/SWI6 repeats, and replacement with a neomycin gene. [MGI Ref ID J:25248]

Genotyping

Genotyping Information

Genotyping Protocols

Notch1^tm1Con, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Conlon RA; Reaume AG; Rossant J. 1995. Notch1 is required for the coordinate segmentation of somites. Development 121(5):1533-45. [PubMed: 7789282]  [MGI Ref ID J:25248]

Additional References

Notch1^tm1Con related

Barrantes IB; Elia AJ; Wunsch K; De Angelis MH; Mak TW; Rossant J; Conlon RA; Gossler A; de la Pompa JL. 1999. Interaction between Notch signalling and Lunatic fringe during somite boundary formation in the mouse. Curr Biol 9(9):470-80. [PubMed: 10330372]  [MGI Ref ID J:54606]

Cheng HT; Kim M; Valerius MT; Surendran K; Schuster-Gossler K; Gossler A; McMahon AP; Kopan R. 2007. Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron. Development 134(4):801-11. [PubMed: 17229764]  [MGI Ref ID J:119907]

Dale JK; Malapert P; Chal J; Vilhais-Neto G; Maroto M; Johnson T; Jayasinghe S; Trainor P; Herrmann B; Pourquie O. 2006. Oscillations of the snail genes in the presomitic mesoderm coordinate segmental patterning and morphogenesis in vertebrate somitogenesis. Dev Cell 10(3):355-66. [PubMed: 16516838]  [MGI Ref ID J:106622]

Ge C; Stanley P. 2010. Effects of varying Notch1 signal strength on embryogenesis and vasculogenesis in compound mutant heterozygotes. BMC Dev Biol 10:36. [PubMed: 20346184]  [MGI Ref ID J:160476]

Girard L; Jolicoeur P. 1998. A full-length Notch1 allele is dispensable for transformation associated with a provirally activated truncated Notch1 allele in Moloney MuLV-infected MMTV(D)/myc transgenic mice. Oncogene 16(4):517-22. [PubMed: 9484841]  [MGI Ref ID J:45669]

Grego-Bessa J; Luna-Zurita L; del Monte G; Bolos V; Melgar P; Arandilla A; Garratt AN; Zang H; Mukouyama YS; Chen H; Shou W; Ballestar E; Esteller M; Rojas A; Perez-Pomares JM; de la Pompa JL. 2007. Notch signaling is essential for ventricular chamber development. Dev Cell 12(3):415-29. [PubMed: 17336907]  [MGI Ref ID J:119151]

Hadland BK; Huppert SS; Kanungo J; Xue Y; Jiang R; Gridley T; Conlon RA; Cheng AM; Kopan R; Longmore GD. 2004. A requirement for Notch1 distinguishes 2 phases of definitive hematopoiesis during development. Blood 104(10):3097-105. [PubMed: 15251982]  [MGI Ref ID J:94898]

Hitoshi S; Alexson T; Tropepe V; Donoviel D; Elia AJ; Nye JS; Conlon RA; Mak TW; Bernstein A; van Der Kooy D. 2002. Notch pathway molecules are essential for the maintenance, but not the generation, of mammalian neural stem cells. Genes Dev 16(7):846-58. [PubMed: 11937492]  [MGI Ref ID J:75878]

Huppert SS; Ilagan MX; De Strooper B; Kopan R. 2005. Analysis of Notch Function in Presomitic Mesoderm Suggests a gamma-Secretase-Independent Role for Presenilins in Somite Differentiation. Dev Cell 8(5):677-88. [PubMed: 15866159]  [MGI Ref ID J:98438]

Huppert SS; Le A; Schroeter EH; Mumm JS; Saxena MT; Milner LA; Kopan R. 2000. Embryonic lethality in mice homozygous for a processing-deficient allele of Notch1. Nature 405(6789):966-70. [PubMed: 10879540]  [MGI Ref ID J:62882]

Kikuchi R; Takeshita K; Uchida Y; Kondo M; Cheng XW; Nakayama T; Yamamoto K; Matsushita T; Liao JK; Murohara T. 2011. Pitavastatin-induced angiogenesis and arteriogenesis is mediated by Notch1 in a murine hindlimb ischemia model without induction of VEGF. Lab Invest 91(5):691-703. [PubMed: 21301413]  [MGI Ref ID J:171259]

Kim YH; Hu H; Guevara-Gallardo S; Lam MT; Fong SY; Wang RA. 2008. Artery and vein size is balanced by Notch and ephrin B2/EphB4 during angiogenesis. Development 135(22):3755-64. [PubMed: 18952909]  [MGI Ref ID J:144857]

Kumano K; Chiba S; Kunisato A; Sata M; Saito T; Nakagami-Yamaguchi E; Yamaguchi T; Masuda S; Shimizu K; Takahashi T; Ogawa S; Hamada Y; Hirai H. 2003. Notch1 but not Notch2 is essential for generating hematopoietic stem cells from endothelial cells. Immunity 18(5):699-711. [PubMed: 12753746]  [MGI Ref ID J:83475]

Li T; Wen H; Brayton C; Das P; Smithson LA; Fauq A; Fan X; Crain BJ; Price DL; Golde TE; Eberhart CG; Wong PC. 2007. Epidermal growth factor receptor and notch pathways participate in the tumor suppressor function of gamma-secretase. J Biol Chem 282(44):32264-73. [PubMed: 17827153]  [MGI Ref ID J:126817]

Liu Z; Obenauf AC; Speicher MR; Kopan R. 2009. Rapid identification of homologous recombinants and determination of gene copy number with reference/query pyrosequencing (RQPS). Genome Res 19(11):2081-9. [PubMed: 19797679]  [MGI Ref ID J:172930]

Loomes KM; Stevens SA; O'brien ML; Gonzalez DM; Ryan MJ; Segalov M; Dormans NJ; Mimoto MS; Gibson JD; Sewell W; Schaffer AA; Nah HD; Rappaport EF; Pratt SC; Dunwoodie SL; Kusumi K. 2007. Dll3 and Notch1 genetic interactions model axial segmental and craniofacial malformations of human birth defects. Dev Dyn 236(10):2943-51. [PubMed: 17849441]  [MGI Ref ID J:125511]

Nakagawa M; Ichikawa M; Kumano K; Goyama S; Kawazu M; Asai T; Ogawa S; Kurokawa M; Chiba S. 2006. AML1/Runx1 rescues Notch1-null mutation-induced deficiency of para-aortic splanchnopleural hematopoiesis. Blood 108(10):3329-34. [PubMed: 16888092]  [MGI Ref ID J:140445]

Nus M; MacGrogan D; Martinez-Poveda B; Benito Y; Casanova JC; Fernandez-Aviles F; Bermejo J; de la Pompa JL. 2011. Diet-induced aortic valve disease in mice haploinsufficient for the Notch pathway effector RBPJK/CSL. Arterioscler Thromb Vasc Biol 31(7):1580-8. [PubMed: 21493891]  [MGI Ref ID J:187551]

Takeshita K; Satoh M; Ii M; Silver M; Limbourg FP; Mukai Y; Rikitake Y; Radtke F; Gridley T; Losordo DW; Liao JK. 2007. Critical role of endothelial Notch1 signaling in postnatal angiogenesis. Circ Res 100(1):70-8. [PubMed: 17158336]  [MGI Ref ID J:130243]

Tan JB; Visan I; Yuan JS; Guidos CJ. 2005. Requirement for Notch1 signals at sequential early stages of intrathymic T cell development. Nat Immunol 6(7):671-9. [PubMed: 15951812]  [MGI Ref ID J:99151]

Thomas JA; Haudek SB; Koroglu T; Tsen MF; Bryant DD; White DJ; Kusewitt DF; Horton JW; Giroir BP. 2003. IRAK1 deletion disrupts cardiac Toll/IL-1 signaling and protects against contractile dysfunction. Am J Physiol Heart Circ Physiol 285(2):H597-606. [PubMed: 12860565]  [MGI Ref ID J:84829]

Timmerman LA; Grego-Bessa J; Raya A; Bertran E; Perez-Pomares JM; Diez J; Aranda S; Palomo S; McCormick F; Izpisua-Belmonte JC; de la Pompa JL. 2004. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev 18(1):99-115. [PubMed: 14701881]  [MGI Ref ID J:87765]

Visan I; Tan JB; Yuan JS; Harper JA; Koch U; Guidos CJ. 2006. Regulation of T lymphopoiesis by Notch1 and Lunatic fringe-mediated competition for intrathymic niches. Nat Immunol 7(6):634-43. [PubMed: 16699526]  [MGI Ref ID J:112675]

de la Pompa JL; Wakeham A; Correia KM; Samper E; Brown S; Aguilera RJ ; Nakano T ; Honjo T ; Mak TW ; Rossant J ; Conlon RA. 1997. Conservation of the Notch signalling pathway in mammalian neurogenesis. Development 124(6):1139-48. [PubMed: 9102301]  [MGI Ref ID J:39351]

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 is maintained by breeding heterozygous mice to normal wildtype siblings or to C57BL/6J inbred mice (Stock No. 000664). Homozygotes die at embryonic day 9.
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

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.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.