STOCK Acvr1b^tm1.1Gsu/J

Stock number: 036934
Product name: Acvr1b^flox
Research areas: Developmental Biology Research, Research Tools

Description

Acvr1b^flox conditional mutant mice possess loxP sites flanking exons 2 and 3 of the Acvr1b (activin A receptor, type 1B) gene and may be useful in generating conditional mutations to study hair follicle development and hair cycling.

Detailed description

Acvr1b (activin A receptor, type 1B) encodes a type I transmembrane serine/threonine kinase receptor that is part of the TGF-β superfamily. The activin signaling pathway has multiple regulatory functions. These conditional Acvr1b mice possess loxP sites flanking exons 2-3. Mice homozygous for the mutation are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 2 and 3 deleted in cre-expressing tissues. Deletion of exons 2 and 3 is expected to result in a frameshift mutation that abolishes Acvr1b expression in a tissue-specific manner. Complete deficiency of Acvr1b results in death during embryogenesis.

For example, when bred to a strain expressing Cre recombinase in skin (such as Tg(KRT14-cre)1Amc, Stock No. 018964) progeny bred to homozygosity become progressively hairless beginning at postnatal day 5. Hair loss is the result of the disruption of hair follicle development and hair cycling.

Development

The targeting construct contains from 5' to 3': a loxP site upstream of exon 2 and an FRT-flanked neomycin cassette followed by a second loxP site downstream of exon 3 of the Acvr1b gene on chromosome 15. The construct was electroporated into 129-derived unspecified embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. Chimeric males were crossed to C57BL/6 females. Offspring were bred with CMV-Flp transgenic mice on an unknown background to delete the neo cassette. The resulting progeny were crossed to remove the Flp-expressing transgene. The strain was backcrossed to C57BL/6J for more than 5 generations by the donating laboratory (see SNP note below). Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

In 20222, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the mice sent to The Jackson Laboratory Repository. Many of the 43 markers throughout the genome were segregating with 129. Also, all 4 of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating, suggesting an incomplete backcross.

Allele

Symbol: Acvr1b^tm1.1Gsu
Name: targeted mutation 1.1, Gloria H Su
MGI accession ID: MGI:5000108
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Acvr1b^flox
Marker symbol: Acvr1b
Marker name: activin A receptor, type 1B
Marker synonyms: ActRIB; ActR-IB; ACVRLK4; ALK4; Skr2
Chromosome: 15
Strain of origin: 129
Molecular note: A loxP site was inserted in intron 1 and an FRT flanked neo cassette and loxP site were inserted in intron 3 via homologous recombination. Flp mediated recombination removed the neo cassette leaving exons 2 and 3 floxed.