JAX Mouse Strain Datasheet - 008602

STOCK Cdon^tm2Rsk/J

Stock No:: 008602

Targeted Mutation

Cryo Recovery

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 (Null/Knockout, Reporter)	Cdon	cell adhesion molecule-related/down-regulated by oncogenes

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Research Applications

Cell Biology Research
Developmental Biology Research
Neurobiology Research
Research Tools

View All Research Applications

Base Price

Starting at:

$2,595.00 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):411-5. PubMed: 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):647-56. PubMed: 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):657-65. PubMed: 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 (Null/Knockout, Reporter)
Allele Synonym(s)	Cdon^lacZ-2
Gene Symbol and Name	Cdon, cell adhesion molecule-related/down-regulated by oncogenes
Gene Synonym(s)	CAM-related/down-regulated by oncogenes; CDO; CDON1; Cdo; HPE11; ORCAM
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
General Note	Phenotypic Similarity to Human Syndrome: Holoprosencephaly in mice homozygous for Cdon^tm2Rsk (J:82221)
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

Research Areas By Genotype

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

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

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
involves: 129/Sv * C57BL/6

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

growth/size/body region phenotype

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

abnormal nasal septum morphology
- nasal septum is reduced in size and there is agenesis or hypoplasia of the nasal septal cartilage

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

abnormal philtrum morphology
- dysgenesis of the philtrum

abnormal primary palate development
- lack a primary palate

decreased body size

craniofacial phenotype

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

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

abnormal nasal septum morphology
- nasal septum is reduced in size and there is agenesis or hypoplasia of the nasal septal cartilage

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

abnormal philtrum morphology
- dysgenesis of the philtrum

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

abnormal primary palate development
- lack a primary palate

basisphenoid bone foramen

small basisphenoid bone

skeleton phenotype

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

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

basisphenoid bone foramen

small basisphenoid bone

respiratory system phenotype

abnormal nasal septum morphology
- nasal septum is reduced in size and there is agenesis or hypoplasia of the nasal septal cartilage

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

digestive/alimentary phenotype

abnormal primary palate development
- lack a primary palate

nervous system phenotype

holoprosencephaly
- microform holoprosencephaly

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

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

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

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

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

holoprosencephaly
- 80-85% develop severe forms of holoprosencephaly

hydroencephaly
- mutants that survive the postnatal period develop hydroencephaly

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

craniofacial phenotype

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

cardiovascular system phenotype

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

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

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

cellular phenotype

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

embryo phenotype

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

References

Cole F; Krauss RS. 2003. Microform Holoprosencephaly in Mice that Lack the Ig Superfamily Member Cdon. Curr Biol 13(5):411-5. PubMed: 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):647-56. PubMed: 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):657-65. PubMed: 16647303 MGI: J:108746

Additional - Cdon^tm2Rsk related

Allen BL; Tenzen T; McMahon AP. 2007. The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse development. Genes Dev 21(10):1244-57. PubMed: 17504941 MGI: J:121553
Camp D; Haitian He B; Li S; Althaus IW; Holtz AM; Allen BL; Charron F; van Meyel DJ. 2014. Ihog and Boi elicit Hh signaling via Ptc but do not aid Ptc in sequestering the Hh ligand. Development 141(20):3879-88. PubMed: 25231763 MGI: J:217507
Cole F; Zhang W; Geyra A; Kang JS; Krauss RS. 2004. Positive regulation of myogenic bHLH factors and skeletal muscle development by the cell surface receptor CDO. Dev Cell 7(6):843-54. PubMed: 15572127 MGI: J:95029
Jeong MH; Kim HJ; Pyun JH; Choi KS; Lee DI; Solhjoo S; O'Rourke B; Tomaselli GF; Jeong DS; Cho H; Kang JS. 2017. Cdon deficiency causes cardiac remodeling through hyperactivation of WNT/beta-catenin signaling. Proc Natl Acad Sci U S A 114(8):E1345-E1354. PubMed: 28154134 MGI: J:240926
Romer AI; Singh J; Rattan S; Krauss RS. 2013. Smooth muscle fascicular reorientation is required for esophageal morphogenesis and dependent on Cdo. J Cell Biol 201(2):309-23. PubMed: 23569214 MGI: J:196678
Zhang W; Mulieri PJ; Gaio U; Bae GU; Krauss RS; Kang JS. 2009. Ocular abnormalities in mice lacking the immunoglobulin superfamily member Cdo. FEBS J 276(20):5998-6010. PubMed: 19754878 MGI: J:156965
Zhang W; Yi MJ; Chen X; Cole F; Krauss RS; Kang JS. 2006. Cortical thinning and hydrocephalus in mice lacking the immunoglobulin superfamily member CDO. Mol Cell Biol 26(10):3764-72. PubMed: 16648472 MGI: J:109070

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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

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

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

mortality/aging

growth/size/body region phenotype

craniofacial phenotype

skeleton phenotype

respiratory system phenotype

digestive/alimentary phenotype

nervous system phenotype

Genotype: Cdontm2Rsk/Cdontm2RskB6.129-Cdontm2Rsk

mortality/aging

nervous system phenotype

craniofacial phenotype

cardiovascular system phenotype

behavior/neurological phenotype

skeleton phenotype

cellular phenotype

embryo phenotype

References

Additional - Cdontm2Rsk related

Genotyping Protocols

Breeding Considerations

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Progeny testing is not required

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Cdon^tm2Rsk

Allele Symbol: Cdon^tm2Rsk

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

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

Additional - Cdon^tm2Rsk related