STOCK Dlk1^tm1.1Jvs/J

Stock number: 019074
Product name: Dlk1^flox
Research areas: Developmental Biology Research, Research Tools

Description

Dlk1^flox mice may be useful for studying Dlk1 function in the development and regeneration of both myogenic progenitor cells and mature skeletal muscles.

Detailed description

These Dlk1^flox mice possess loxP sites flanking the last two exons of the delta-like 1 homolog (Dlk1) gene. Dlk1 is an epidermal growth factor (EGF)-like protein expressed from the paternal allele in skeletal muscle and cartilage. Expression is also seen in the developing pituitary gland, pancreas, lung, adrenal gland, and placenta. Since Dlk1 is paternally inherited, the donating investigator maintains these mice as heterozygotes, with the mutated allele always originating from the male parent.

When Dlk1^flox are bred to mice that express Cre recombinase, resulting offspring will have the last two exons deleted in cre-expressing tissues. Because Dlk1 is imprinted and only expressed from the paternal allele, breeding Dlk1^flox males with Cre-expressing females is required to generate deleted offspring with the knockout phenotype.
For example, when Dlk1^flox males are crossed to females expressing Cre recombinase in muscle progenitor cells (Stock No. 007893 B6.129S4-Myf5^tm3(cre)Sor/J), the resulting mice exhibit defective muscle development, elevated inflammatory responses, and delayed muscle regeneration.

Development

A targeting vector was designed by Dr. Jennifer Schmidt (University of Illinois at Chicago) to surround the last 2 exons of the delta-like 1 homolog (Dlk1) gene with loxP sites. A neomycin resistance (neo) cassette followed by a single loxP site was inserted downstream of the final exon. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. The resulting mice were bred to C57BL/6J mice and their offspring were bred to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J (Stock No. 003724) transgenic mice. Offspring contained multiple gene rearrangments; intact floxed-exons, intact floxed-neo cassette, or excision of both floxed-exons and the neo cassette. Male Dlk1^flox offspring, containing only the floxed-exons, were bred with C57BL/6J females. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Dlk1^tm1.1Jvs
Name: targeted mutation 1.1, Jennifer V Schmidt
MGI accession ID: MGI:4879107
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Dlk1
Marker name: delta like non-canonical Notch ligand 1
Chromosome: 12
Strain of origin: 129P2/OlaHsd
Molecular note: A loxP site and a neo cassette flanked by two loxP sites were inserted to flank the last two exons (5 and 6). The neo cassette was removed in vivo by Cre-mediated recombination.