STOCK Senp2^tm3.1Whsu/J

Stock number: 039991
Product name: SENP2Fx
Research areas: Cell Biology Research, Developmental Biology Research, Research Tools

Description

SENP2Fx mice have loxP sites flanking exon 4 of the Senp2 gene. These mice may be useful when studying the role of SUMO modification during embryogenesis.

Detailed description

SENP2Fx mice have loxP sites flanking exon 4 of the SUMO/sentrin specific peptidase 2 (Senp2) gene. Senp2 encodes an enzyme that processes newly synthesized small ubiquitin-related modifier (SUMO) into the conjugatable form and also catalyzes the deconjugation of SUMO-containing species. Deconjugation of SUMO from its substrates is essential for development of trophoblast stem cells, niches and lineages. Global deletion of SENP2 leads to midgestational lethality, and causes severe defects in the placenta which is accompanied by embryonic brain and heart abnormalities.

Homozygous mice are viable and fertile. When bred to EIIa-Cre (Stock No. 003724)??? mice, germline deletion of exon 4 creates an out of frame deletion and no protein is detected. Resulting homozygous SENP2^-/- embryos die by E11.5. Placentas are smaller and paler than the controls. Histological evaluations revealed severe abnormalities in all three major trophoblast layers.

When bred to Tie2-Cre (Stock No. 008863) mice, endothelial-specific disruption of SENP2 in resulting SENP2^Tie2 mice leads to no obvious defects in heart phenotype when compared to control mice at E10.5 and SENP2^Tie2 mice were born alive.

Of note, SENP2^ΔSUMOFx mice (Stock No. 039992) have exon 16 floxed. This region encodes a protease core domain which leads to Cre-inducible expression of a truncated mutant protein that is SUMO protease activity deficient.

Development

The SENP2Fx targeting vector was designed to insert a loxP site upstream of exon 4 of the SUMO/sentrin specific peptidase 2 (Senp2) gene, and a loxP-flanked neomycin resistance (neo) cassette was inserted downstream of exon 4. The construct was electroporated into 129S6/SvEvTac-derived CSL3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the chimeric mice were bred to EIIa-Cre mice (Stock No. 003724) to remove the neo cassette. Resulting SENP2Fx offspring were bred to C57BL/6J mice (Stock No. 000664) and were further maintained on a mixed genetic background by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Senp2^tm3.1Whsu
Name: targeted mutation 3.1, Wei Hsu
MGI accession ID: MGI:7718780
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: SENP2Fx; Senp3^f
Marker symbol: Senp2
Marker name: SUMO/sentrin specific peptidase 2
Marker synonyms: 2310007L05Rik; 4930538C18Rik; Axam; AXAM2; mKIAA1331; SMT3IP2
Chromosome: 16
Strain of origin: 129S6/SvEvTac
Molecular note: A loxP site was inserted in intron 3 and a floxed pgk-neo cassette was inserted in intron 4 via homologous recombination. Cre mediated recombination removed the neo cassette leaving exon 4 floxed.