B6N.129P2-Axin2^tm1Wbm/J

Stock number: 009120
Product name: Conductin^lacZ
Research areas: Cell Biology Research, Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research, Research Tools, Sensorineural Research

Description

The Axin2^lacZ mutation both abolishes endogenous gene function and expresses NLS-lacZ under the control of the endogenous promoter/enhancer regions. Homozygous mice exhibit a phenotype resembling craniosynostosis in humans.

Detailed description

Homozygous mice are viable and fertile, with the Axin2^lacZ (or conductin^lacZ) mutation that both abolishes endogenous Axin2 gene function and expresses NLS-lacZ under the control of the endogenous Axin2 promoter/enhancer regions. Homozygous mice exhibit cranial skull defects and malformations of skull structures; a phenotype resembling craniosynostosis in humans. Specifically, homozygous mice show an obvious reduction in head growth within the first 3 weeks after birth, resulting from developmental defects of the cranial skull (premature fusion of cranial sutures) at early postnatal stages. Axin2-deficient mice have abnormal calvarial morphogenesis/osteoblast development. Because Axin2 is a negative regulator of the canonical Wnt pathway that suppress signal transduction by promoting β-catenin degradation, the NLS-lacZ expression in these Axin2^lacZ (or conductin^lacZ) mutant mice may be useful in monitoring endogenous canonical Wnt signals in many tissues and organs during development, regeneration and tumorigenesis.

C57BL/6N-derived mice are homozygous for the recessive mutation retinal degeneration 8 (Crb1^rd8) - identified as a single base deletion in the Crb1 gene that causes a frame shift and premature stop codon that truncates the transmembrane and cytoplasmic domain of the protein. Mice homozygous for Crb1^rd8 exhibit retinal external limiting membrane fragmentation and outer retinal dysplasia, as well as multifocal retinal degeneration and the accumulation of subretinal microglia/macrophages [Mattapallil et al. 2012 Invest Ophthalmol Vis Sci. 53:2921 , Mehalow et al. 2003 Hum Mol Genet. 12:2179 , Luhmann et al. 2012 PLoS One 7:e35551]. Of note, C57BL/6J-derived mice are homozygous for the wildtype Crb1 allele.

Development

A targeting vector was used delete most of exon 2 of the Axin2 (Axin2/conductin/Axil) locus via in-frame insertion of a nuclear-localized β-galactosidase (NLS-lacZ) gene (followed by a polyA signal and neo cassette) into the endogenous Axin2 start codon. This construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. ES cells were injected into recipient blastocysts, and chimeric mice were bred with C57BL/6NCrl mice to establish the mutant colony. The donating investigator reports that mutant mice were subsequently backcrossed to C57BL/6NCrl inbred mice for 15 generations prior to sending to The Jackson Laboratory Repository in 2009. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304).
Of note, it is not known if the Y chromosome has been fixed to the C57BL/6N background during backcrossing.

Allele

Symbol: Axin2^tm1Wbm
Name: targeted mutation 1, Walter Birchmeier
MGI accession ID: MGI:3579503
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Axin2
Marker name: axin 2
Chromosome: 11
Strain of origin: 129P2/OlaHsd
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: LacZ with a nuclear localization signal (NLS-lacZ) replaces expression of the targeted gene and may be useful in monitoring endogenous canonical Wnt signals in many tissues during development, regeneration and tumorigenesis.
Molecular note: A lacZ gene containing a nuclear localization signal was introduced in frame to the endogenous start codon by homologous recombination, thereby replacing most of exon 2. Beta-galactosidase staining reflected endogenous gene expression in the developing embryo.