B6;129P2-Sumf1^{Gt(RST760)Byg}/ClearJ

Stock number: 030711
Product name: Sumf1 KO
Research areas: Apoptosis Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools

Description

These Sumf1 genetrap/knock-out mice lack sulfatase activity, exhibit growth retardation, premature lethality, glycosaminoglycan accumulation, inflammation and neuronal loss. They are suitable for use in applications related to the study of mucosulfatidosis.

Detailed description

The targeted Sumf1 gene encodes an enzyme responsible for post-translational modification of the active site of sulfatases. Mutations in this gene have been associated with the lysosomal storage disorder, multiple sulfatase deficiency.

These mice carry a β-geo genetrap/knockout mutation located in intron 3 of the mouse Sumf1 gene, which produces a fusion transcript. RT-PCR shows that the fusion transcript is made up of the first 3 exons fused to β-geo. The fusion transcript is detected by RT-PCR in liver and brain from homozygotes; no wildtype transcript was detected. Homozygotes do not exhibit sulfatase activity in MEFs, liver, kidney or brain tissue. Heterozygotes are viable and fertile. Homozygous mice exhibit growth retardation, craniofacial and skeletal abnormalities, neurological defects, and most die prematurely (10% reach 3 months of age). By 1 month of age homozygotes develop hind limb clasping, tremors (head) and seizures. Accumulation of glycosaminoglycan in macrophage infiltration of tissues progresses with age. Progressive Purkinje cell loss and astroglyosis is detected in brain. Homozygotes, at 2 and 6 months of age, display increased levels of apoptosis and proapoptotic and inflammatory cytokines in brain and liver.

Development

A gene trap vector containing a splice-acceptor sequence upstream of β-geo (a fusion of ß-galactosidase and neomycin phosphotransferase II) was introduced to intron 3 of the gene. This mutation was created in 129P2/OlaHsd-derived E14TG2a.4 (or CGR8) embryonic stem (ES) cells. Correctly-targeted RST760 ES cells were injected into C57BL/6 blastocysts, and chimeric mice were bred with C57BL/6 mice. The mice were backcrossed to C57BL/6J for 3 generations.

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).

Allele

Symbol: Sumf1^{Gt(RST760)Byg}
Name: gene trap RST760, BayGenomics
MGI accession ID: MGI:3707232
Generation method: Gene trapped
Attributes: Reporter; Null/Knockout
Synonyms: Sumf1^-
Marker symbol: Sumf1
Marker name: sulfatase modifying factor 1
Marker synonyms: AAPA3037; FGE; UNQ3037
Chromosome: 6
Strain of origin: 129P2/OlaHsd
Expressed genes: Bgeo,fusion of beta-galactosidase and neomycin phosphotransferase genes,E. coli
Site of expression: The β-geo fusion transcript is detected by RT-PCR in liver and brain from homozygotes.
Molecular note: A gene trap vector was inserted into intron 3. RT-PCR demonstrated that the fusion transcript was composed by the first three exons of the locus and beta-geo.
General note: ES cells used are CGR8 or E14TG2