STOCK Tmpo^tm1.2Foi/J

Stock number: 036903
Product name: Lap2α^fl
Strain synonyms: Lap2α^flΔNeo
Research areas: Cell Biology Research, Research Tools

Description

Lap2α^fl mice have loxP sites flanking exon 4 of the Tmpo gene. This mutant mouse strain may be useful in studies of chromatin regulation, cell cycle regulation, epidermal proliferation and differentiation, and laminopathic diseases.

Detailed description

Lap2α^fl mice have loxP sites flanking exon 4 of the thymopoietin (Tmpo) gene. Lap2α encodes a member of the LAP2 protein family, members of which are involved in a variety of cellular functions including gene expression, chromatin organization, and replication and cell cycle control. Specifically, LAP2α localizes to the interior of the nucleus where it is involved in the structural organization of the nucleus and of chromatin in the post-mitotic nuclear assembly. Mutations in Lap2α have been associated with cardiac disorders, as well as hyperproliferation of tissue progenitor cells and tissue hyperplasia due to defects in cell cycle exit.

Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 4 removed in the Cre-expressing tissues of the offspring.

Of note, Stock No. 010828 contains a full knock-out of this floxed allele.

Development

The Lap2α^fl targeting vector was designed to insert a loxP site, followed by a frt-flanked neomycin resistance cassette, upstream of exon 4 of the thymopoietin (Tmpo) gene. A second loxP site was inserted downstream of exon 4. The construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺ derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred with ACTB:FLPe mice to remove the neo cassette. Resulting offspring were crossed to remove the Flpe expressing transgene, and mice were subsequently backcrossed to C57BL/6NCrl for at least 10 generations by the donating laboratory (see SNP note below). Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304).

In 2021, 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 males sent to The Jackson Laboratory Repository. Many of the 43 markers throughout the genome were segregating with 129 and SJL on multiple chromosomes, suggesting an incomplete backcross.

Allele

Symbol: Tmpo^tm1.2Foi
Name: targeted mutation 1.2, Roland Foisner
MGI accession ID: MGI:6810743
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Lap2alpha^fl
Marker symbol: Tmpo
Marker name: thymopoietin
Marker synonyms: 5630400D24Rik; CMD1T; lamina-associated polypeptide 2; LAP2; LEMD4; PRO0868; TP
Chromosome: 10
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: At least six alternative transcripts can be derived from this gene locus. This mutation targeted exon 4, which is necessary for generation of a protein product that localizes to the nucleoplasm. A loxP site and a FRT-flanked neomycin cassette was placed upstream of exon 4 and an additional loxP site was placed downstream of the exon. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exon 4 floxed.