Overview

Also Known As:129/Sv-Cdo, 129/Sv-Cdon

Homozygous Cdon^lacZ-2 (or Cdo^lacZ-2) mice harbor a beta-galactosidase (lacZ) "knock-in" mutation that also abolishes expression of the targeted Cdon (cell adhesion molecule-related/down-regulated by oncogenes) gene. This strain may be useful in studying holoprosencephaly (HPE; a common defect of human forebrain development), craniofacial/brain development and the regulation of Sonic Hedgehog (Shh) signaling pathways.

Donating Investigator

Robert S Krauss, Mount Sinai School of Medicine

Genetic overview

Genetic Background	Generation

Cdon^tm2Rsk

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Cdon	cell adhesion molecule-related/down-regulated by oncogenes

View Genetics

Research Applications

Research Tools
Developmental Biology Research
Cell Biology Research
Neurobiology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Homozygous Cdon^lacZ-2 (or Cdo^lacZ-2) mice on a "129/Sv" genetic background are viable and fertile, harboring a beta-galactosidase (lacZ) "knock-in" mutation that also abolishes targeted gene expression. LacZ expression mimics the pattern observed for the endogenous gene. On a 129/Sv background, Cdo-deficient mice exhibit craniofacial midline defects identified as microforms of holoprosencephaly (HPE; a common defect of human forebrain development) with partial penetrance, grossly normal limb development and no perinatal lethality. These Cdon^lacZ-2 (or Cdo^lacZ-2) mice are a genetic model of HPE and may be useful in studying craniofacial/brain development and the regulation of Sonic Hedgehog (Shh) signaling pathways, as well as for lacZ expression in Cdo-expressing tissues.

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. It should be noted that the phenotype of these mutant mice could vary from that originally described. For example, the penetrance and expressivity of HPE phenotypes for Cdo-deficient mice is dependent upon genetic background: homozygotes on the C57BL/6 genetic background display severe semilobar HPE and cebocephaly and perinatal lethality with high penetrance, while homozygotes on a mixed 129/Sv x C57BL/6 genetic background display craniofacial microforms of HPE with high penetrance and partial perinatal lethality.

Development

A targeting vector was designed to insert an IRES-lacZ reporter gene (internal ribosome entry site, beta-galactosidase, GTI-2 promoter-neo cassette and polyA sequence) into the third coding exon of the targeted gene. The donating investigator reports that the construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells, and chimeric males were bred with 129S6/SvEvTac females to obtain mutant animals. These mutant mice were maintained mostly by heterozygous intercross (with some wildtype or 129S6/SvEvTac or C57BL/6 breedings possible as well) for many generations prior to arrival at The Jackson Laboratory. Upon arrival at The Jackson Laboratory, these mice were bred to 129S1/SvImJ inbred mice (Stock No. 002448) for at least one generation to establish the colony.

A 27 SNP (single nucleotide polymorphism) panel analysis with markers covering all 19 chromosomes and the X chromosome was performed on the rederived living colony at The Jackson Laboratory Repository. Although some mice were homozygous 129S1/129S6/129X1 allele-type for all 27 markers, some littermates had one marker on chromosome 2 and one marker on chromosome 11 that were heterozygous for 129 or C57BL/6 allele-type. This suggests some outcrossing to non-129 mice occurred prior (possibly many generations prior) to arrival and cryopreservation at The Jackson Laboratory Repository.

Expression Data

Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	LacZ expression replaces the pattern observed for the endogenous targeted gene, including the embryonic forebrain.

Control Suggestions

Wild-type from the colony

Approximate Controls

002448 129S1/SvImJ

Additional Information

Considerations for Choosing Controls

Selected References

Cole F; Krauss RS. 2003. Microform Holoprosencephaly in Mice that Lack the Ig Superfamily Member Cdon. Curr Biol 13(5):411-5PubMed: 12620190 MGI: J:82221
Tenzen T; Allen BL; Cole F; Kang JS; Krauss RS; McMahon AP. 2006. The cell surface membrane proteins Cdo and Boc are components and targets of the Hedgehog signaling pathway and feedback network in mice. Dev Cell 10(5):647-56PubMed: 16647304 MGI: J:108747
Zhang W; Kang JS; Cole F; Yi MJ; Krauss RS. 2006. Cdo functions at multiple points in the Sonic Hedgehog pathway, and Cdo-deficient mice accurately model human holoprosencephaly. Dev Cell 10(5):657-65PubMed: 16647303 MGI: J:108746

View All References

Genetics

Cdon^tm2Rsk

Allele Symbol: Cdon^tm2Rsk

Allele Name	targeted mutation 2, Robert S Krauss
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	Cdon^lacZ-2
Gene Symbol and Name	Cdon, cell adhesion molecule-related/down-regulated by oncogenes
Gene Synonym(s)
Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	LacZ expression replaces the pattern observed for the endogenous targeted gene, including the embryonic forebrain.
Strain of Origin	129/Sv
Chromosome	9
Molecular Note	An IRES-lacZ-neo cassette was inserted at the 3' terminus of exon 3. Endogenous protein was undetected by Western blot analysis of homozygous mutant mice. Beta-galactosidase activity was detected by staining.
Mutations Made By	Robert Krauss, Mount Sinai School of Medicine

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

holoprosencephaly 11

Research Areas By Phenotype

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

Research Tools
- lacZ Expression
- Genetics Research
  - Tissue/Cell Markers
Developmental Biology Research
- Craniofacial and Palate Defects
- Internal/Organ Defects
  - brain
Cell Biology Research
- Signal Transduction
Neurobiology Research
- lacZ expression in neural tissue

Mammalian Phenotype Terms by Genotype

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

Genotype: Cdon^tm2Rsk/Cdon^tm2Rsk
B6.129-Cdon

behavior/neurological phenotype

weakness
- mutants that survive the postnatal period show limb weakness and immobility

skeleton phenotype

domed cranium
- mutants that survive the postnatal period have a dome-shaped head

cardiovascular system phenotype

hemorrhage
- mutants that survive the postnatal period have brains that display surface bleeding

abnormal blood vessel morphology
- dilated blood vessels in the enlarged forebrain

cellular phenotype

abnormal neuronal precursor proliferation
- primary neural progenitor cells from E14.5 cortices display a reduced proliferation rate

craniofacial phenotype

domed cranium
- mutants that survive the postnatal period have a dome-shaped head

embryo phenotype

absent lamina terminalis
- the dorsal midline of cortices exhibit an abnormal structure, lacking the lamina terminalis

mortality/aging

perinatal lethality, incomplete penetrance
- homozygotes that develop holoprosencephaly (80-85%) die perinatally

premature death
- 15 to 20% do not exhibit overt signs of holoprosencephaly and survive beyond the perinatal period, but die within 4-12 weeks of birth

nervous system phenotype

abnormal brain ventricle morphology

abnormal cerebral cortex morphology
- the dorsal midline of cortices exhibit an abnormal structure, lacking the lamina terminalis

abnormal forebrain morphology
- mutants that survive the postnatal period exhibit an enlarged gap between the hypothalamus and pons, indicating a slight truncation of the forebrain
- mutants that survive the postnatal period exhibit highly enlarged forebrains with dilated blood vessels and olfactory bulbs

holoprosencephaly
- 80-85% develop severe forms of holoprosencephaly

hydrocephaly
- mutants that survive the postnatal period develop hydroencephaly

abnormal neuronal precursor proliferation
- primary neural progenitor cells from E14.5 cortices display a reduced proliferation rate

enlarged lateral ventricles
- mutants that survive the postnatal period have enlarged lateral ventricles with a disruption of the septum, consistent with hydrocephalus

thin cerebral cortex
- the posterior telencephalon of E18.5 brains shows a translucent appearance, indicating thinning of the cortex
- variable severity of cortical thinning; mutants with holoprosencephaly exhibit the most severe thinning

absent lamina terminalis
- the dorsal midline of cortices exhibit an abnormal structure, lacking the lamina terminalis

Genotype: Cdon^tm2Rsk/Cdon^tm2Rsk
involves: 129/Sv * C57BL/6

craniofacial phenotype

small basisphenoid bone

abnormal premaxilla morphology
- fusion of the premaxillary bone, resulting in severe pyriform aperture stenosis

absent nasal septum cartilage
- agenesis or hypoplasia of the nasal septal cartilage

abnormal philtrum morphology
- dysgenesis of the philtrum

absent upper incisors
- maxillary incisors are sometimes absent

nasal septum cartilage hypoplasia
- agenesis or hypoplasia of the nasal septal cartilage

small nasal septum
- nasal septum is reduced in size

abnormal nose morphology
- increase in presumptive mesenchyme between the nasal capsule and the oral cavity
- although medial nasal process (MNP) fusion occurs normally at E11.5, later stage embryos maintain an epithelialized furrow at the MNP midline and have a recessed inferior border

basisphenoid bone foramen

abnormal craniofacial morphology
- about 95% of mutants exhibit craniofacial abnormalities

piriform aperture stenosis
- fusion of the premaxillary bone, resulting in severe pyriform aperture stenosis

abnormal upper incisor morphology
- mutants either have a single, central maxillary incisor or no maxillary incisors

absent primary palate
- lack a primary palate

digestive/alimentary phenotype

absent primary palate
- lack a primary palate

growth/size/body region phenotype

abnormal upper incisor morphology
- mutants either have a single, central maxillary incisor or no maxillary incisors

nasal septum cartilage hypoplasia
- agenesis or hypoplasia of the nasal septal cartilage

abnormal philtrum morphology
- dysgenesis of the philtrum

decreased body size

abnormal nose morphology
- although medial nasal process (MNP) fusion occurs normally at E11.5, later stage embryos maintain an epithelialized furrow at the MNP midline and have a recessed inferior border
- increase in presumptive mesenchyme between the nasal capsule and the oral cavity

absent upper incisors
- maxillary incisors are sometimes absent

piriform aperture stenosis
- fusion of the premaxillary bone, resulting in severe pyriform aperture stenosis

absent primary palate
- lack a primary palate

small nasal septum
- nasal septum is reduced in size

absent nasal septum cartilage
- agenesis or hypoplasia of the nasal septal cartilage

mortality/aging

neonatal lethality, incomplete penetrance
- exhibit a similar range and frequency of neonatal lethality as Cdon^tm1Rsk homozygotes

postnatal lethality, incomplete penetrance
- exhibit a similar range and frequency of lethality as Cdon^tm1Rsk homozygotes

nervous system phenotype

holoprosencephaly
- microform holoprosencephaly

respiratory system phenotype

abnormal nose morphology
- increase in presumptive mesenchyme between the nasal capsule and the oral cavity
- although medial nasal process (MNP) fusion occurs normally at E11.5, later stage embryos maintain an epithelialized furrow at the MNP midline and have a recessed inferior border

piriform aperture stenosis
- fusion of the premaxillary bone, resulting in severe pyriform aperture stenosis

small nasal septum
- nasal septum is reduced in size

absent nasal septum cartilage
- agenesis or hypoplasia of the nasal septal cartilage

nasal septum cartilage hypoplasia
- agenesis or hypoplasia of the nasal septal cartilage

skeleton phenotype

abnormal premaxilla morphology
- fusion of the premaxillary bone, resulting in severe pyriform aperture stenosis

absent upper incisors
- maxillary incisors are sometimes absent

nasal septum cartilage hypoplasia
- agenesis or hypoplasia of the nasal septal cartilage

abnormal upper incisor morphology
- mutants either have a single, central maxillary incisor or no maxillary incisors

absent nasal septum cartilage
- agenesis or hypoplasia of the nasal septal cartilage

small basisphenoid bone

basisphenoid bone foramen

References

Cole F; Krauss RS. 2003. Microform Holoprosencephaly in Mice that Lack the Ig Superfamily Member Cdon. Curr Biol 13(5):411-5PubMed: 12620190 MGI: J:82221
Tenzen T; Allen BL; Cole F; Kang JS; Krauss RS; McMahon AP. 2006. The cell surface membrane proteins Cdo and Boc are components and targets of the Hedgehog signaling pathway and feedback network in mice. Dev Cell 10(5):647-56PubMed: 16647304 MGI: J:108747
Zhang W; Kang JS; Cole F; Yi MJ; Krauss RS. 2006. Cdo functions at multiple points in the Sonic Hedgehog pathway, and Cdo-deficient mice accurately model human holoprosencephaly. Dev Cell 10(5):657-65PubMed: 16647303 MGI: J:108746

Additional - Cdon^tm2Rsk related

Technical Support

CONTACT TECHNICAL SUPPORT

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

When maintaining a live colony of Cdon^lacZ-2 on the 129/Sv genetic background, the donating investigator breeds heterozygous mice together.
- Additional Breeding and Husbandry Support
Citation
When using the STOCK Cdon^tm2Rsk/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008602 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 Cdon<tm2Rsk>

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

Also Known As:129/Sv-Cdo, 129/Sv-Cdon

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Cdontm2Rsk

Allele Symbol: Cdontm2Rsk

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Cdontm2Rsk/Cdontm2RskB6.129-Cdon

behavior/neurological phenotype

skeleton phenotype

cardiovascular system phenotype

cellular phenotype

craniofacial phenotype

embryo phenotype

mortality/aging

nervous system phenotype

Genotype: Cdontm2Rsk/Cdontm2Rskinvolves: 129/Sv * C57BL/6

craniofacial phenotype

digestive/alimentary phenotype

growth/size/body region phenotype

mortality/aging

nervous system phenotype

respiratory system phenotype

skeleton phenotype

References

Additional - Cdontm2Rsk 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

Cdon^tm2Rsk

Allele Symbol: Cdon^tm2Rsk

Genotype: Cdon^tm2Rsk/Cdon^tm2Rsk
B6.129-Cdon

Genotype: Cdon^tm2Rsk/Cdon^tm2Rsk
involves: 129/Sv * C57BL/6

Additional - Cdon^tm2Rsk related