Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Heterozygote         (Female x Male) Species laboratory mouse Generation N13F1pF3 (12-NOV-08)   Donating Investigator Nora Heisterkamp,   Childrens Hospital Los Angeles

Description
While heterozygous mice are viable and fertile, mice homozygous for this targeted allele die in utero. Immunoblots from homozygous tissues show no protein expression from the targeted gene. The prenatal lethality exhibited by homozygotes on this C57BL/6J congenic background (and also on a 129Sv genetic background) likely results from heart, liver, and placental defects. Please note that homozygous mutants on a mixed/outbred genetic background (129/Sv X Black Swiss) are viable and fertile. These mutant mice may be useful in studying the role of Crkl tyrosine-phosphorylation in Bcr/Abl (Philadelphia chromosome) chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), Digeorge Syndrome (DGS) and Velocardiofacial Syndrome.

Development
A targeting vector was designed to replace a portion of exon 1 of the targeted gene with a neomycin resistance cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were microinjected into blastocysts, and chimeric offspring were bred to 129X1/SvJ mice. Heterozygous mutants were then backcrossed to C57BL/6J for at least 12 generations prior to arrival at The Jackson Laboratory.

Control Information

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

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Crkl^tm1Hkp/Crkl^tm1Hkp

        involves: 129S1/Sv * 129X1/SvJ * Black Swiss

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:76680)
  • mutants with decreased birth weight have an increased chance of dying within the first 4 days of life, however those that survive are viable and fertile unlike mutants on a 129/Sv background which die during embryogenesis
• growth/size phenotype
• decreased body weight (MGI Ref ID J:76680)
  • lower birth weight, however surviving mutants reach the same weight and size by 6 months of age
• cardiovascular system phenotype
• abnormal heart septum morphology (MGI Ref ID J:76680)
  • some mutants have a small septum defect in the heart
• limbs/digits/tail phenotype
• abnormal caudal vertebrae morphology (MGI Ref ID J:76680)
  • tail vertebra show an irregular, wedge-like shape and the lateral borders are fused to each other on one side, resulting in kinks
• kinked tail (MGI Ref ID J:76680)
  • 53% of pups at birth have bent or curved tails
• skeleton phenotype
• abnormal caudal vertebrae morphology (MGI Ref ID J:76680)
  • tail vertebra show an irregular, wedge-like shape and the lateral borders are fused to each other on one side, resulting in kinks

Crkl^tm1Hkp/Crkl^tm1Hkp

        involves: 129S1/Sv * 129X1/SvJ

• lethality-prenatal/perinatal
• prenatal lethality (MGI Ref ID J:76680)
  • die during embryogenesis unlike on a Black Swiss background in which mutants are viable
• embryogenesis phenotype
• abnormal placenta morphology (MGI Ref ID J:76680)
  • placental defects
• cardiovascular system phenotype
• abnormal heart morphology (MGI Ref ID J:76680)
  • heart defects
• liver/biliary system phenotype
• abnormal liver morphology (MGI Ref ID J:76680)
  • liver defects

View Research Applications

Research Applications

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

Cancer Research
Chronic Myelogenous Leukemia

Cell Biology Research
Signal Transduction

Developmental Biology Research
Embryonic Lethality (Homozygous)
Internal/Organ Defects (heart)
Internal/Organ Defects (liver)

Immunology and Inflammation Research
Intracellular Signaling Molecules

Research Tools
Cancer Research (Leukemia)
Cell Biology Research
Developmental Biology Research
Immunology and Inflammation Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Crkltm1Hkp
Allele Name		targeted mutation 1, Nora Heisterkamp
Allele Type		Targeted (knock-out)
Common Name(s)		crkl-;
Mutation Made By		Nora Heisterkamp,   Childrens Hospital Los Angeles
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		Crkl, v-crk sarcoma virus CT10 oncogene homolog (avian)-like
Chromosome		16
Gene Common Name(s)		1110025F07Rik; AA589403; AI325100; Crkol; RIKEN cDNA 1110025F07 gene; expressed sequence AA589403; expressed sequence AI325100;
Molecular Note		A portion of exon 1 was replaced with a neomycin selection cassette inserted by homologous recombination. [MGI Ref ID J:76680]

Genotyping

Genotyping Information

Genotyping Protocols

Crkl^tm1Hkp, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Hemmeryckx B; Reichert A; Watanabe M; Kaartinen V; de Jong R; Pattengale PK; Groffen J; Heisterkamp N. 2002. BCR/ABL P190 transgenic mice develop leukemia in the absence of Crkl. Oncogene 21(20):3225-31. [PubMed: 12082638]  [MGI Ref ID J:76680]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, heterozygous mice may be bred to wildtype siblings or C57BL/6J inbred mice. Homozygous mice on this genetic background die in utero.
Mating System	+/+ sibling x Heterozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

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.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Tel: 800.422.6423 or 207.288.5845
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

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

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.