B6.Cg-Axin1^Fu-Tg1/CosMmjax

Stock number: 008885
Research areas: Apoptosis Research, Cardiovascular Research, Cell Biology Research, Developmental Biology Research, Internal/Organ Research, Neurobiology Research, Research Tools

Description

The Axin^Tg1 transgenic insertional allele has the ~600 kb human epsilon-globin gene inserted between exon 1 and exon 3 (deleting exon 2) of the Axin1 locus. The transgene directs expression of truncated Axin1 mRNA product (still containing exons 3-10) that results in a recessive loss-of-function allele.

Detailed description

The Axin^Tg1 transgenic insertional allele (previously called Fu^Tg1 or Hε46) has a tandem array of the human epsilon-globin gene (~600 kb in total) inserted between exon 1 and exon 3 (deleting exon 2) of the Axin1 locus. The transgene directs expression of a truncated Axin1 mRNA product (still containing exons 3-10) that results in a recessive loss-of-function allele. Homozygous Axin^Tg1 mice die between embryonic day (E)8-E10 with abnormalities in developmental patterning (duplication of embryonic axis and parts of the embryo) and nervous system development (truncated headfolds, severely underdeveloped/absent forebrain, and kinked neural tube). Some incidence of cardia bifida and enlarged pericardium are reported in severely affected homozygotes. These Axin^Tg1 mutant mice may be useful for studying developmental patterning, axis duplication, forebrain development, negative regulation of canonical Wnt signaling pathway, β-catenin/cadherin function, and apoptosis.

Development

An 8.1 kb transgene harboring a tandem array of the human epsilon-globin gene (~600 kb in total) was microinjected into (CBA/J x C57BL/6J)F2 zygotes, and founder mice were bred to (CBA/J x C57BL/6J)F1 mice. Transgenic founder line 46 (Hε46) was established on a CBA/J;C57BL/6J hybrid background and found to have the transgene inserted between exon 1 and exon 3 of the Axin1 locus; also resulting in deletion of exon 2 and parts of the two flanking introns. Mice heterozygous for this Axin^Tg1 transgenic insertional allele (previously called Fu^Tg1 or Hε46), were backcrossed to C57BL/6J inbred mice for approximately 20 generations by the laboratory of Dr. Frank Costantini (Columbia University Medical Center). Heterozygous embryos were then cryopreserved. Aliquots of these frozen embryos were sent to Mutant Mouse Regional Resource Center node at The Jackson Laboratory (Mmjax) and used to establish a live mutant colony.

Allele

Symbol: Axin1^Fu-Tg1
Name: fused transgenic 1
MGI accession ID: MGI:1857546
Generation method: Transgenic
Marker symbol: Axin1
Marker name: axin 1
Chromosome: 17
Strain of origin: (CBA/J x C57BL/6J)F2
Molecular note: In this mutation, an ~600 kb transgene is inserted between exons 1 and 3, and exon 2 and 20 kb from the two flanking introns are deleted. This disruption results in the absence of the major wild-type 3.9 kb mRNA in homozygotes.