Strain Name:

CB6-Isl1tm1Tmj/J

Stock Number:

009645

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Homozygous Isl1 (ISL1 transcription factor, LIM/homeodomain) targeted mutation embryos are arrested in their development soon after embryonic day 9.5 (E9.5) and demonstrate abnormalities in the organization of the vascular endothelium and its surrounding mesenchyme. Motor neurons are not generated without ISL1 protein and a population of interneurons that express engrailed 1 (EN1) also fails to differentiate in these mutant embryos.

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 Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating Investigator Samuel Pfaff,   The Salk Institute

Description
Homozygous embryos are arrested in their development soon after embryonic day 9.5 (E9.5) but exhibit an overtly normal organization of neural, mesodermal, and endodermal tissues. Histological analysis of embryos reveals abnormalities in the organization of the vascular endothelium and its surrounding mesenchyme, notably a disruption in the formation of the dorsal aorta. An impairment in vascular development is therefore a possible cause of the embryonic lethality in homozygous mutants. Motor neurons are not generated without ISL1 protein, although many other aspects of cell differentiation in the neural tube occur normally. A population of interneurons that express engrailed 1 (EN1), however, also fails to differentiate in these mutant embryos. ISL1 is required for the generation of motor neurons and motor neuron generation is required for the subsequent differentiation of certain interneurons.

Homozygote embryos analyzed at E9.5 express a modified transcript in mesodermal cells, but no expression is detected in neural tissues. No ISL1 immunoreactivity is detected in any tissues in homozygous mutant embryos, indicating that the targeted mutation eliminates expression of ISL1 protein.

Development
Exon 3 (LIM domain 2) of the gene was replaced by a neomycin resistance cassette. The targeting vector was electroporated into 129S1/Sv Oca2+ Tyr+ Kitl +-derived W9.5/W95 embryonic stem (ES) cells. The line was initially backcrossed to C57BL/6 and then to CB6F1/J mice for 12 years by the donating laboratory.

Related Strains

Strains carrying other alleles of Isl1
024242   STOCK Isl1tm1(cre)Sev/J
017952   STOCK Tg(Isl1-EGFP*)1Slp/J
View Strains carrying other alleles of Isl1     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Isl1tm1Tmj/Isl1tm1Tmj

        either: 129S1/Sv-Isl1tm1Tmj or (involves: 129S1/Sv * C57BL/6J)
  • mortality/aging
  • complete embryonic lethality during organogenesis
    • die by E11.5   (MGI Ref ID J:31131)
  • growth/size/body phenotype
  • decreased embryo size
    • embryos are smaller by E9-9.5   (MGI Ref ID J:31131)
  • embryogenesis phenotype
  • decreased embryo size
    • embryos are smaller by E9-9.5   (MGI Ref ID J:31131)
  • decreased embryonic neuroepithelium thickness
    • exhibit marked thinning of the neuroepithelium in the ventral neural tube   (MGI Ref ID J:31131)
  • embryo tissue necrosis
    • embryos are necrotic at E11.5   (MGI Ref ID J:31131)
  • embryonic growth arrest
    • E10.5 embryos show no advance in development compared with E9.5, indicating arrested development soon after E9.5   (MGI Ref ID J:31131)
  • nervous system phenotype
  • abnormal motor neuron morphology
    • motor neuron differentiation does not occur at E9.5 in the hindbrain and spinal cord, however notochord, floorplate and neural tube differentiation appear normal   (MGI Ref ID J:31131)
    • isolated neural tube segments do not generate motor neurons in culture, indicating an inability, not a delay, of neural progenitors to generate motor neurons   (MGI Ref ID J:31131)
    • exhibit a marked increase in the incidence of apoptotic cell death in the ventral neural tube, the region in which motor neurons normally are generated   (MGI Ref ID J:31131)
    • exhibit an approximately 73% decrease in mitotic cells in the ventral neural tube, indicating decreased cell proliferation of cells that give rise to motor neurons   (MGI Ref ID J:31131)
  • abnormal spinal cord interneuron morphology
    • engrailed1 positive interneurons are absent in the neural tube of 25 somite stage embryos   (MGI Ref ID J:31131)
    • cultured cervical neural tube explants to not form interneurons, indicating a failure, and not a delay, of interneuron differentiation   (MGI Ref ID J:31131)
  • decreased embryonic neuroepithelium thickness
    • exhibit marked thinning of the neuroepithelium in the ventral neural tube   (MGI Ref ID J:31131)
  • cardiovascular system phenotype
  • abnormal dorsal aorta morphology
    • dorsal aorta formation is disrupted at E9.5-10.5   (MGI Ref ID J:31131)
  • abnormal vascular endothelial cell morphology
    • exhibit abnormalities in the organization of the vascular endothelium and its surrounding mesenchyme at E9.5-10.5   (MGI Ref ID J:31131)

Isl1tm1Tmj/Isl1tm1Tmj

        involves: 129S1/Sv
  • mortality/aging
  • complete embryonic lethality during organogenesis
    • die around E10.5   (MGI Ref ID J:95093)
  • embryogenesis phenotype
  • abnormal pharyngeal arch morphology
    • exhibit decreased cell proliferation in pharyngeal endoderm   (MGI Ref ID J:95093)
  • abnormal splanchnic mesoderm morphology
    • exhibit decreased cell proliferation and increased apoptosis of splanchnic mesodermal cells that are immediately adjacent to pharyngeal endoderm at E8.75 or E9.5   (MGI Ref ID J:95093)
  • embryonic growth arrest
    • growth retardation at about E9.5   (MGI Ref ID J:95093)
  • cardiovascular system phenotype
  • abnormal heart atrium morphology
    • exhibit significant reduction in the amount of atrial tissue   (MGI Ref ID J:95093)
  • abnormal heart development
    • cardiac primorida at E8.75 resembles cardiac primordia seen in wild-type at E8.25, suggesting an interruption in heart development   (MGI Ref ID J:95093)
    • failure of heart looping
      • hearts are unlooped at E9-9.5   (MGI Ref ID J:95093)
  • abnormal heart shape
    • hearts are misshapen at E9-9.5   (MGI Ref ID J:95093)
  • abnormal outflow tract development
    • lack an outflow tract as indicated by marker analysis   (MGI Ref ID J:95093)
  • absent heart right ventricle
    • lack the right ventricle, although cells with left ventricular, A/V canal and atrial identities are present   (MGI Ref ID J:95093)
  • digestive/alimentary phenotype
  • abnormal pancreatic acinar cell morphology
    • exhibit failure of exocrine cell differentiation in the dorsal but not the ventral pancreas   (MGI Ref ID J:37641)
  • endocrine/exocrine gland phenotype
  • abnormal pancreas morphology   (MGI Ref ID J:37641)
    • abnormal pancreas mesenchyme morphology
      • dorsal pancreatic mesenchyme does not form   (MGI Ref ID J:37641)
    • abnormal pancreatic acinar cell morphology
      • exhibit failure of exocrine cell differentiation in the dorsal but not the ventral pancreas   (MGI Ref ID J:37641)
    • abnormal pancreatic islet morphology
      • cultured gut explants do not generate differentiated islet cells   (MGI Ref ID J:37641)
      • absent pancreatic alpha cells
        • exhibit complete absence of islet (glucogon+) cells in E9.5 embryos   (MGI Ref ID J:37641)
  • abnormal pituitary diverticulum morphology
    • rudimentary pouch forms at E9.5, small and primitive   (MGI Ref ID J:50517)
    • pouch cells are aberrant and fail to differentiate   (MGI Ref ID J:50517)
  • craniofacial phenotype
  • abnormal pharyngeal arch morphology
    • exhibit decreased cell proliferation in pharyngeal endoderm   (MGI Ref ID J:95093)
  • nervous system phenotype
  • abnormal pituitary diverticulum morphology
    • rudimentary pouch forms at E9.5, small and primitive   (MGI Ref ID J:50517)
    • pouch cells are aberrant and fail to differentiate   (MGI Ref ID J:50517)
View Research Applications

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

Developmental Biology Research
Embryonic Lethality (Homozygous)

Neurobiology Research
Neurodevelopmental Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Isl1tm1Tmj
Allele Name targeted mutation 1, Thomas M Jessell
Allele Type Targeted (Null/Knockout)
Common Name(s) Isl1delta;
Mutation Made By Thomas Jessell,   Columbia University/HHMI
Strain of Origin129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line NameW9.5/W95
ES Cell Line Strain129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name Isl1, ISL1 transcription factor, LIM/homeodomain
Chromosome 13
Gene Common Name(s) ISLET1; Isl-1; Islet 1;
Molecular Note A neomycin selection cassette was inserted such that the exon encoding the second LIM domain was deleted and that splicing from the exon encoding the first LIM domain to the exon encoding the homeodomain would result in a frameshift mutation. In situ hybridization did not detect transcript produced from this allele in the neural tube of homzygous mutant mice, but message was detected in the mesoderm ventral to the neural tube. Immunohistochemical analysis of homozygous mutant embryonic sections showed a lack of protein in all analyzed tissues. [MGI Ref ID J:31131]

Genotyping

Genotyping Information


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Pfaff SL; Mendelsohn M; Stewart CL; Edlund T; Jessell TM. 1996. Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation. Cell 84(2):309-20. [PubMed: 8565076]  [MGI Ref ID J:31131]

Additional References

Isl1tm1Tmj related

Ahlgren U; Pfaff SL; Jessell TM; Edlund T; Edlund H. 1997. Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Nature 385(6613):257-60. [PubMed: 9000074]  [MGI Ref ID J:37641]

Cai CL; Liang X; Shi Y; Chu PH; Pfaff SL; Chen J; Evans S. 2003. Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell 5(6):877-89. [PubMed: 14667410]  [MGI Ref ID J:95093]

Herrera PL; Nepote V; Delacour A. 2002. Pancreatic cell lineage analyses in mice. Endocrine 19(3):267-78. [PubMed: 12624426]  [MGI Ref ID J:126939]

Song MR; Sun Y; Bryson A; Gill GN; Evans SM; Pfaff SL. 2009. Islet-to-LMO stoichiometries control the function of transcription complexes that specify motor neuron and V2a interneuron identity. Development 136(17):2923-32. [PubMed: 19666821]  [MGI Ref ID J:152175]

Sun Y; Dykes IM; Liang X; Eng SR; Evans SM; Turner EE. 2008. A central role for Islet1 in sensory neuron development linking sensory and spinal gene regulatory programs. Nat Neurosci 11(11):1283-93. [PubMed: 18849985]  [MGI Ref ID J:141110]

Takuma N; Sheng HZ; Furuta Y; Ward JM; Sharma K; Hogan BL; Pfaff SL; Westphal H; Kimura S; Mahon KA. 1998. Formation of Rathke's pouch requires dual induction from the diencephalon. Development 125(23):4835-40. [PubMed: 9806931]  [MGI Ref ID J:50517]

Thaler JP; Koo SJ; Kania A; Lettieri K; Andrews S; Cox C; Jessell TM; Pfaff SL. 2004. A postmitotic role for Isl-class LIM homeodomain proteins in the assignment of visceral spinal motor neuron identity. Neuron 41(3):337-50. [PubMed: 14766174]  [MGI Ref ID J:89755]

Westerlund J; Andersson L; Carlsson T; Zoppoli P; Fagman H; Nilsson M. 2008. Expression of Islet1 in thyroid development related to budding, migration, and fusion of primordia. Dev Dyn 237(12):3820-9. [PubMed: 18985716]  [MGI Ref ID J:143212]

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 & HusbandryWhen maintained as a live colony, heterozygotes may be bred. Homozygotes are embryonic lethal.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

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.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

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.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

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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.
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