B6;129-Sirt1^tm1Ygu/J

Stock number: 008041
Product name: SirT1^co
Research areas: Cancer Research, Cell Biology Research, Diabetes and Obesity Research, Endocrine Deficiency Research, Research Tools

Description

These SirT1^co/co mice may be useful in generating conditional mutations for studying the role of estrogen, insulin growth factor-1 (IGF-1), and transcription factors (including NF-kappaB) in mammary gland development, breast cancer, apoptosis, and metabolic diseases.

Detailed description

Mice homozygous for this targeted allele (SirT1^co/co) are viable and fertile. A loxP-flanked neomycin cassette just upstream of exon 4 and a third loxP site downstream of exon 4 were inserted to create this targeted mutant Sirt1 allele. The floxed mutation does not affect SIRT1 protein expression in MEFs or mammary gland tissue in homozygotes. When bred to mice that express Cre recombinase, the resulting offspring have exon 4 (encoding an evolutionarily conserved Sir2 motif) deleted in cre-expressing tissue(s); (the donating investigator reports only one recombination event: complete removal of the neomycin cassette and exon 4, leaving a single loxp). These SirT1^co/co mice may be useful in generating conditional mutants for studying transcriptional regulation and the role of estrogen, insulin growth factor-1 (IGF-1), and transcription factors (including NF-kappaB) in mammary gland development, mammary cancer, apoptosis, and metabolic diseases.

Development

A targeting vector was designed to insert a loxP-flanked, reverse-oriented neomycin cassette just upstream of exon 4 and a third loxP site downstream of exon 4 of the targeted gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the chimeras were bred with C57BL/6 mice. The resulting heterozygotes were interbred to generate homozygous SirT1^co/co mice on this mixed B6;129 genetic background. Homozygotes were interbred for many generations prior to arrival at The Jackson Laboratory.

Allele

Symbol: Sirt1^tm1Ygu
Name: targeted mutation 1, Yansong Gu
MGI accession ID: MGI:3764971
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Sirt1
Marker name: sirtuin 1
Chromosome: 10
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A floxed neomycin cassette was inserted just upstream of exon 4 and a third loxP site was inserted just downstream. The floxed mutation does not affect the protein expression of the targeted gene in MEF's or mammary tissue from homozygotes. When bred to mice that express Cre recombinase, the resulting offspring will have exon 4 (encoding a conserved Sir2 motif) deleted in the cre-expressing tissue(s).