STOCK Cdon^tm2Rsk/J

Stock number: 008602
Strain synonyms: 129/Sv-Cdo, 129/Sv-Cdon
Research areas: Cell Biology Research, Developmental Biology Research, Neurobiology Research, Research Tools

Description

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.

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.

Allele

Symbol: Cdon^tm2Rsk
Name: targeted mutation 2, Robert S Krauss
MGI accession ID: MGI:2653132
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Synonyms: Cdon^lacZ-2
Marker symbol: Cdon
Marker name: cell adhesion molecule-related/down-regulated by oncogenes
Marker synonyms: CAM-related/down-regulated by oncogenes; Cdo; CDON1; HPE11; Ihog; ORCAM
Chromosome: 9
Strain of origin: 129/Sv
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: LacZ expression replaces the pattern observed for the endogenous targeted gene, including the embryonic forebrain.
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.