B6.129-Sumo2^tm1Weiy/J

Stock number: 031690
Product name: SUMO2 null
Research areas: Cancer Research, Cardiovascular Research, Cell Biology Research, Developmental Biology Research, Research Tools

Description

SUMO2 null mice may be useful for studying the role of SUMO conjugation and global SUMOylation in embryonic development.

Detailed description

SUMOylation is the process by which small ubiquitin-like modifiers (SUMOs) are covalently conjugated to lysine residues of target proteins - thereby modulating their function, stability and localization. SUMO conjugation modulates many cellular functions including DNA repair, genome maintenance, gene transcription and protein degradation control, and plays key roles in many human diseases such as cerebral ischemia/stroke, cancer and heart failure.
SUMO1, SUMO2 and SUMO3 are widely expressed in mammalian tissues. SUMO2 and SUMO3 are almost identical (proteins differ by only three amino acids) and are often referred to collectively as SUMO2/3.

The Jackson Laboratory Repository has mice with the SUMO2 knock-out allele (Stock No. 031690) or the SUMO3 knock-out allele (Stock No. 031691). Both mouse lines are described below.

Stock No. 031690: The SUMO2 knock-out allele has 2 premature stop codons and a neo cassette inserted just downstream of the endogenous Sumo2 ATG codon. Whole-mount in situ hybridization analysis of homozygous mutant embryos confirmed that this is a functionally null allele. Mice heterozygous for the SUMO2 knock-out allele (SUMO2^+/-) are viable and fertile, with normal fertility and no gross physical, motor or behavioral abnormalities. Mice homozygous for the SUMO2 knock-out allele (SUMO2^-/-) are embryonic lethal - with complete penetrance of in utero death around embryonic day (E)10.5.

Stock No. 031691: The SUMO3 knock-out allele has 2 premature stop codons and a neo cassette inserted just downstream of the endogenous Sumo3 ATG codon. Whole-mount in situ hybridization analysis of homozygous mutant embryos confirmed that this is a functionally null allele. Both SUMO3 knock-out heterozygotes (SUMO3^+/-) and homozygotes (SUMO3^-/-) are viable and fertile, with normal fertility and no gross physical, motor or behavioral abnormalities.

Of note, the donating investigator also characterized the phenotype of SUMO2/3 double mutant animals. Mice heterozygous for both knock-out alleles (SUMO2^+/-;SUMO3^+/-) are viable and fertile with no overt phenotype. However, mice heterozygous for SUMO2 knock-out and homozygous for SUMO3 knock-out (SUMO2^+/-;SUMO3^-/-) are potentially lethal at late stage embryogenesis.

Development

The SUMO2 knock-out allele was created by Dr. Wei Yang (Duke University Medical Center).

A targeting vector was designed to insert (in-frame) two premature stop codons and a neomycin resistance cassette (neo) downstream of the ATG codon in exon 1 of the small ubiquitin-like modifier 2 gene (Sumo2) on chromosome 11.

The construct was electroporated into 129Sv-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and chimeric animals were bred with C57BL/6J mice for germline transmission.

The resulting mice with the SUMO2 knock-out allele were backcrossed to C57BL/6J inbred mice for more than ten generations, and then heterozygous males with black coat color were sent to The Jackson Laboratory Repository in 2018.

Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).


Of note, the donating investigator reports that, at least once during backcrossing, a heterozygous female was bred to a C57BL/6J inbred male (thus the Y chromosome of the congenic strain is of C57BL/6J origin).

Allele

Symbol: Sumo2^tm1Weiy
Name: targeted mutation 1, Wei Yang
MGI accession ID: MGI:5641883
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Sumo2^-
Marker symbol: Sumo2
Marker name: small ubiquitin-like modifier 2
Marker synonyms: AABR07034657.1; HSMT3; Smt3A; SMT3B; SMT3H2; Sumo2l
Chromosome: 11
Strain of origin: 129
Molecular note: Exon 1 was disrupted by in-frame insertion of two premature stop codons and a neomycin resistance cassette downstream of the ATG codon. Whole-mount in situ hybridization analysis of homozygous mutant embryos confirmed that this is a functionally null allele.