Overview

Mice homozygous for this targeted mutation of Sloan-Kettering viral oncogene homolog (Ski) die before or shortly after birth due to developmental defects. Homozygotes on the A/J background exhibit exencephaly (severe neural tube closure defects), with a higher embryonic lethality than homozygotes on the C57BL/6 or 129 backgrounds. None exhibit facial clefting. None exhibit facial clefting. This mutant strain may be useful in studies of facial cleft formation, 1p36 deletion syndrome, oncogene function, apoptosis, and neural tube and skeletal muscle defects.

Donating Investigator

Clemencia Colmenares, The Cleveland Clinic Foundation

Genetic overview

Genetic Background	Generation

Ski^tm1Cco

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ski	ski sarcoma viral oncogene homolog (avian)

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Research Applications

Developmental Biology Research
Sensorineural Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the targeted mutation die before or shortly after birth due to
developmental defects. Homozygotes on the A/J background exhibit exencephaly (severe
neural tube closure defects), with a higher embryonic lethality than homozygotes on the
C57BL/6 or 129 backgrounds. None exhibit facial clefting. The Donating Investigator reports that homozygotes display flattened or shorter snouts, iris malformation and polydactyly. The penetrance of the phenotype
is highly background dependent. Heterozygotes are viable and fertile with timely cranial
neural tube closure, and a low incidence of facial clefting. The Donating Investigator reports some heterozygotes on the A/J background exhibit lateral facial clefting. This mutant strain may be useful
in studies of facial cleft formation, 1p36 deletion syndrome, oncogene function, apoptosis,
and neural tube and skeletal muscle defects.

Development

A targeting vector containing a thymidine kinase-driven neomycin resistance cassette was used to disrupt exon 1 and generated a small deletion in the coding sequence. The construct was electroporated into 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric mice were bred to 129S6Tac (129P3) and then backcrossed to A/J for 9 generations before arriving at The Jackson Laboratory. After arriving, the mice were crossed to A/J once.

Control Suggestions

Wild-type from the colony
000646 A/J

Additional Information

Considerations for Choosing Controls

Selected References

Berk M; Desai SY; Heyman HC; Colmenares C. 1997. Mice lacking the ski proto-oncogene have defects in neurulation, craniofacial, patterning, and skeletal muscle development. Genes Dev 11(16):2029-39PubMed: 9284043 MGI: J:42573

View All References

Genetics

Ski^tm1Cco

Allele Symbol: Ski^tm1Cco

Allele Name	targeted mutation 1, Clemencia Colmenares
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	ski-
Gene Symbol and Name	Ski, ski sarcoma viral oncogene homolog (avian)
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	4
Molecular Note	Insertion of a neomycin resistance cassette into the exon 1 generated a small deletion in the coding sequence.
Mutations Made By	Clemencia Colmenares, The Cleveland Clinic Foundation

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Developmental Biology Research
- Skeletal Defects
  - polydactyly
- Craniofacial and Palate Defects
  - congenital cleft palate
  - cleft palate and cleft lip
- Eye Defects
- Neural Tube Defects
- Embryonic Lethality (Homozygous)
  - incomplete
- Perinatal Lethality
  - Homozygous
Sensorineural Research
- Olfaction
- Eye Defects
Neurobiology Research
- Neural Tube Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Ski^tm1Cco/Ski⁺
involves: 129P2/OlaHsd * Black Swiss

craniofacial phenotype

midline facial cleft
- frontonasal clefting occasionally seen

embryo phenotype

abnormal neural tube morphology

growth/size/body region phenotype

midline facial cleft
- frontonasal clefting occasionally seen

nervous system phenotype

abnormal neural tube morphology

exencephaly
- occasional exencephally seen

Genotype: Ski^tm1Cco/Ski^tm1Cco
involves: 129P2/OlaHsd * Black Swiss

cardiovascular system phenotype

hemorrhage
- in E18.5 embryos delivered by cesarean, severe hemorrhage occurs from exposed brain mass

embryo phenotype

open neural tube
- no caudal neural tube defects, spina bifida or kinky tails
- excessive apoptosis at E9.5 but not at E10.5
- occurs in about 85% of embryos
- defect at the level of the midbrain-forebrain boundary and extending forward and backward or in one or the other direction

abnormal paraxial mesoderm morphology
- mesenchyme adjacent to neural tube was somewhat disorganized

abnormal ectomesenchyme morphology
- excessive apoptosis in craniofacial mesenchyme at E9.5 but not E10.5

cellular phenotype

increased fibroblast proliferation
- increased rate of proliferation for MEF in culture

growth/size/body region phenotype

flat face
- facial flattening

decreased fetal size
- E18.5 pups delivered by cesarean were 10% smaller than normal

abnormal ectomesenchyme morphology
- excessive apoptosis in craniofacial mesenchyme at E9.5 but not E10.5

midline facial cleft
- frontonasal clefting found in 15% of pups and E18.5 embryos

limbs/digits/tail phenotype

polydactyly
- vestigial hexadactyly

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance
- occurs between E9.5 and E14.5
- moderate

perinatal lethality, complete penetrance
- homozygotes dead at birth
- E18.5 pups born live by cesarean died shortly after birth

muscle phenotype

abnormal skeletal muscle fiber morphology
- fibers were shorter and somewhat disorganized

decreased skeletal muscle mass

decreased skeletal muscle fiber diameter
- reduced diameter of muscle fibers

abnormal skeletal muscle morphology
- increased space between muscle fibers

muscle hypoplasia
- on a Swiss Black background, 15% extremely emaciated and 20% somewhat skinny

nervous system phenotype

open neural tube
- occurs in about 85% of embryos
- no caudal neural tube defects, spina bifida or kinky tails
- defect at the level of the midbrain-forebrain boundary and extending forward and backward or in one or the other direction
- excessive apoptosis at E9.5 but not at E10.5

abnormal olfactory bulb morphology
- malformed olfactory bulb

exencephaly
- exposed brain mass normally sheared off in normal birth

abnormal forebrain morphology
- ventral midline fusion of the forebrain

skeleton phenotype

abnormal cervical atlas morphology

mandibular hyperostosis
- mandibular bone is thick

short mandible
- mandibular bone is short

abnormal cervical axis morphology

abnormal spine curvature
- abnormal curvature of the back, head and neck

vertebral transformation
- homeotic transformations unless facial clefting is present

abnormal skeleton development

absent parietal bone
- loss of parietal bones

absent frontal bone
- loss of frontal bones

abnormal cervical vertebrae morphology
- first three cervical vertebrae affected

abnormal jaw morphology
- abnormal square jaw

absent interparietal bone
- loss of interparietal bones

small basisphenoid bone
- basisphenoid is small and malformed

abnormal neurocranium morphology

abnormal presphenoid bone morphology
- presphenoid is always absent or abnormal

small basioccipital bone
- basioccipital bones are small and malformed

vision/eye phenotype

eyelids open at birth
- homozygotes are born with their eyes open

craniofacial phenotype

absent parietal bone
- loss of parietal bones

flat face
- facial flattening

abnormal presphenoid bone morphology
- presphenoid is always absent or abnormal

small basioccipital bone
- basioccipital bones are small and malformed

abnormal neurocranium morphology

absent interparietal bone
- loss of interparietal bones

small basisphenoid bone
- basisphenoid is small and malformed

mandibular hyperostosis
- mandibular bone is thick

short mandible
- mandibular bone is short

abnormal jaw morphology
- abnormal square jaw

absent frontal bone
- loss of frontal bones

midline facial cleft
- frontonasal clefting found in 15% of pups and E18.5 embryos

Genotype: Ski^tm1Cco/Ski^tm1Cco
involves: 129P2/OlaHsd * C57BL/6

craniofacial phenotype

midline facial cleft
- While the phenotype expressed on this background is essentially the same as that on a 129P2 and Black Swiss background, as backcrossing to C57BL/6 continues the frequency of facial clefts increases

growth/size/body region phenotype

midline facial cleft
- While the phenotype expressed on this background is essentially the same as that on a 129P2 and Black Swiss background, as backcrossing to C57BL/6 continues the frequency of facial clefts increases

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance
- Background Sensitivity - while the phenotype expressed on this background is essentially the same as that on a 129P2 and Black Swiss background, embryonic lethality was delayed to between E14.5 and E18.5
- while the phenotype expressed on this background is essentially the same as that on a 129P2 and Black Swiss background, embryonic lethality was delayed to between E14.5 and E18.5

muscle phenotype

muscle hypoplasia
- While the phenotype expressed on this background is essentially the same as that on a 129P2 and Black Swiss background, on a C57BL/6 background 50-60% of homozygous mice were obviously skinny with flaccid limbs

nervous system phenotype

exencephaly
- While the phenotype expressed on this background is essentially the same as that on a 129P2 and Black Swiss background, continued backcrossing to C57BL/6 reduces frequency of exencephaly

Genotype: Ski^tm1Cco/Ski⁺
involves: 129P2/OlaHsd * C57BL/6

cellular phenotype

increased fibroblast proliferation
- In addition to the phenotype observed for heterozygotes on a 129P2 and Black Swiss background, heterozygotes on this background display increased rate of proliferation for MEF in culture

homeostasis/metabolism phenotype

increased incidence of tumors by chemical induction
- n addition to the phenotype observed for heterozygotes on a 129P2 and Black Swiss background, heterozygotes on this background display increased succeptibility for tumors when injected IP with 9,10-dimethyl-1,2-benzanthracene

neoplasm

increased incidence of tumors by chemical induction
- n addition to the phenotype observed for heterozygotes on a 129P2 and Black Swiss background, heterozygotes on this background display increased succeptibility for tumors when injected IP with 9,10-dimethyl-1,2-benzanthracene

increased lymphoma incidence
- the most frequent tumors to develop were malignant lymphomas

References

Berk M; Desai SY; Heyman HC; Colmenares C. 1997. Mice lacking the ski proto-oncogene have defects in neurulation, craniofacial, patterning, and skeletal muscle development. Genes Dev 11(16):2029-39PubMed: 9284043 MGI: J:42573

Additional - Ski^tm1Cco related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Ski
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes die before or shortly after birth.
- Additional Breeding and Husbandry Support
Citation
When using the A.129P-Ski^tm1Cco/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #009092 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous or Wild-type for Ski<tm1Cco>

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.

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Skitm1Cco

Allele Symbol: Skitm1Cco

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Skitm1Cco/Ski+involves: 129P2/OlaHsd * Black Swiss

craniofacial phenotype

embryo phenotype

growth/size/body region phenotype

nervous system phenotype

Genotype: Skitm1Cco/Skitm1Ccoinvolves: 129P2/OlaHsd * Black Swiss

cardiovascular system phenotype

embryo phenotype

cellular phenotype

growth/size/body region phenotype

limbs/digits/tail phenotype

mortality/aging

muscle phenotype

nervous system phenotype

skeleton phenotype

vision/eye phenotype

craniofacial phenotype

Genotype: Skitm1Cco/Skitm1Ccoinvolves: 129P2/OlaHsd * C57BL/6

craniofacial phenotype

growth/size/body region phenotype

mortality/aging

muscle phenotype

nervous system phenotype

Genotype: Skitm1Cco/Ski+involves: 129P2/OlaHsd * C57BL/6

cellular phenotype

homeostasis/metabolism phenotype

neoplasm

References

Additional - Skitm1Cco related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Ski^tm1Cco

Allele Symbol: Ski^tm1Cco

Genotype: Ski^tm1Cco/Ski⁺
involves: 129P2/OlaHsd * Black Swiss

Genotype: Ski^tm1Cco/Ski^tm1Cco
involves: 129P2/OlaHsd * Black Swiss

Genotype: Ski^tm1Cco/Ski^tm1Cco
involves: 129P2/OlaHsd * C57BL/6

Genotype: Ski^tm1Cco/Ski⁺
involves: 129P2/OlaHsd * C57BL/6

Additional - Ski^tm1Cco related