B6.Cg-Serpina3c^tm1.1Chao/J

Stock number: 032328
Product name: KS^fl [floxed exon 3]
Research areas: Cancer Research, Neurobiology Research, Research Tools

Description

KS^fl mice have loxP sites flanking exon 3 of the kallistatin-encoding gene (Serpina3c). Cre recombinase-mediated removal of the floxed sequence creates the predicted kallistatin knock-out allele. These KS^fl mice may be useful in studying oxidative stress, inflammation, apoptosis, fibrosis, angiogenesis, cancer, tumors, vascular injury and cardiovascular disease.

Detailed description

Kallistatin (KS; encoded by the Serpina3c gene) was identified in plasma as a tissue kallikrein-binding protein and a serine proteinase inhibitor. KS exerts pleiotropic effects on oxidative stress, inflammation, apoptosis, fibrosis, angiogenesis and tumor growth. Specifically, KS functions to protect against vascular injury and senescence by inhibiting oxidative stress and inflammation. KS may also function in aging (leukocyte telomere length), cardiovascular disease, diabetic retinopathy, inflammatory bowel disease and pneumonia.

The KS^fl allele has loxP sites flanking Serpina3c exon 3. Mice heterozygous or homozygous for this floxed allele are viable and fertile with normal breeding, and no reported gross physical or behavioral abnormalities.

Upon exposure to Cre recombinase, the floxed region is deleted - creating the predicted kallistatin knock-out allele (KS^del).
For example, when KS^fl are bred to germline Cre recombinase-expressing mice (CAGGCre-ER^TM; Stock No. 004682) and subjected to tamoxifen, the resulting global null homozygotes (CAGCre⁺;KS^fl/fl) have systemic kallistatin-deficiency (as shown via genotyping and reduced mouse kallistatin protein levels in kidney).
In addition, when KS^fl are bred to Tie2-Cre transgenic mice (Stock No. 008863), the resulting endothelial-specific kallistatin knock-out mice (KS^endo-/- or Tie2Cre⁺KS^fl/fl) allow study of the role of kallistatin in diabetes-associated endothelial senescence, oxidative stress and inflammation. [Guo et al. 2018 J Cell Mol Med 22:4387]

Development

The kallistatin floxed (KS^fl) allele was created for Dr. Julie Chao (Medical University of South Carolina). First, a targeting vector was designed to have a loxP site upstream of exon 3, and an FRT-flanked neo cassette followed by a loxP site just downstream of exon 3 of the serine (or cysteine) peptidase inhibitor, clade A, member 3C locus (Serpina3c ; kallistatin) on chromosome 12. The construct was electroporated into unspecified embryonic stem cells. Chimeric animals were bred to unspecified mice for germline transmission. At some point, exposure to Flp recombinase led to permanent removal of the neo cassette. Mice retaining the loxP-flanked exon 3 allele (with the neo removed) were selected and called KS^fl. The donating investigator reports they maintained the KS^fl colony (on C57BL/6J genetic background) as homozygotes prior to sending KS^fl males with black coat color 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, it is not known if the Y chromosome has been fixed to the C57BL/6J background during backcrossing.

Allele

Symbol: Serpina3c^tm1.1Chao
Name: targeted mutation 1.1, Julie Chao
MGI accession ID: MGI:6200073
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: KS^fl
Marker symbol: Serpina3c
Marker name: serine (or cysteine) peptidase inhibitor, clade A, member 3C
Marker synonyms: 1A1; AACT; Ab1-021; ACT; alpha-1 antiproteinase; CPi-21; CPi-23; GHR-P63; GIG24; GIG25; Kalbp; Kbp; Klkbp; Serpina3k; SPI1; SPI2; SPI-2; SPI-2.3; Spin1; Spin2; Spin2a; Spin2b
Chromosome: 12
Strain of origin: Not Specified
Molecular note: The targeting vector is designed to have a loxP site upstream of exon 3, and an FRT-flanked neo cassette followed by a loxP site just downstream of exon 3 of the gene. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exon 3 floxed.