B6;129S6-Rr23^tm1Axvi/Mmjax

Stock number: 022358
Strain synonyms: Enhancer HS746KO
Research areas: Developmental Biology Research

Description

In this knockout of the non-coding enhancer element (Rr23or HS746), mRNA expression of Msx1 in mouse embryos is diminished and adult skulls exhibit significant differences in skull morphology. This strain may be useful for downstream analysis of craniofacial development.

Detailed description

The regulatory region 23 (Rr23 or HS746) is a non-coding enhancer element that controls expression of Msx1 (homeobox, msh-like 1), a gene involved in craniofacial development. qPCR analysis indicates a 1.5 fold down regulation of Msx1 in homozygous HS1431 E11.5 and E13.5 embryos. Analysis of the adult skulls from homozygous mice by micro-computed tomography reveals significant differences in skull morphology compared to wild type. Alterations in HS746 include a shortening of the face, a widening of the posterior neurocranium, a narrowing of the palate and shortening of the cranial base. This strain may be useful for downstream analysis of craniofacial development.

Development

A targeting vector containing a loxP-flanked PGKneo cassette was used to delete 1682 bp of the HS746 enhancer sequence. Transient Cre expression in targeted cells excised the neo cassette. The construct was electroporated into 129S6/SvEvTac-derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice for approximately three generations. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Allele

Symbol: Rr23^tm1Axvi
Name: targeted mutation 1, Axel Visel
MGI accession ID: MGI:5470292
Generation method: Targeted
Attributes: Null/Knockout; No functional change
Marker symbol: Rr23
Marker name: regulatory region 23
Chromosome: 5
Strain of origin: 129S6/SvEvTac
Molecular note: Msx1 enhancer HS746, located 235 kb downstream inside Stx18 intron 1, was replaced with a loxP site flanked neomycin selection cassette which was subsequently removed by cre excision.