129S.129P2(B6)-Crebbp^tm1Pkb/J

Stock number: 025530
Research areas: Cell Biology Research

Description

These mice carry point mutations (Tyr650Ala, Leu653Leu-Ala654Gln and Tyr658Ala) in the KIX transcription factor-binding region of the mouse Crebbp gene. This strain is useful in studies of transcriptional regulation.

Detailed description

Crebbp (CREB binding protein, also known as CBP) is a protein acetyltransferase that is required for normal development. It interacts with a significant percentage of mammalian transcriptional regulatory proteins and mutations in the gene have been found in hematopoietic and epithelial tumors.

This strain carries point mutations (Tyr650Ala, Leu653Leu-Ala654Gln and Tyr658Ala) in the protein-binding KIX domain of the mouse Crebbp gene. Homozygotes are viable and fertile, and unlike mutations in the KIX domain of Ep300 gene (see Stock No. 025170 and Stock No. 025528), do not exhibit a hematopoietic phenotype. Homozygotes tend to be smaller than their heterozygous and wildtype littermates and show a slight reduction in thymocyte numbers.

Development

Tyr650Ala (TAT->GCT), Leu653Leu Ala654Gln (TTA GCA->CTG CAG, producing a PstI restriction site), and Tyr658Ala (TAT->GCT mutations were introduced to the KIX domain encoded by exon 10 and a loxP-flanked neomycin cassette was placed in an upstream intron through homologous recombination in 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Transient expression of cre recombinase in the ES cells was done to excise the neomycin cassette. Resultant chimeric mice were crossed with C57BL/6J animals, then to 129P2/Ola for 7 generations. Fertility/productivity issues precipitated 23 generations of backcrossing to 129S2/SvPasCrl by the donating laboratory.

Allele

Symbol: Crebbp^tm1Pkb
Name: targeted mutation 1, Paul K Brindle
MGI accession ID: MGI:3578129
Generation method: Targeted
Attributes: Not Specified
Marker symbol: Crebbp
Marker name: CREB binding protein
Chromosome: 16
Strain of origin: 129P2/OlaHsd
Molecular note: A floxed neomycin selection cassette was inserted upstream of the exon encoding the KIX domain and the KIX containing exon itself was mutated so that the tyrosine at amino acid residue 650 became alanine, the alanine at residue 654 became glutamine and the tyrosine at residue 658 became alanine (Y650A, A654Q and Y658A). Transient cre expression then excised the selection cassette. Expression and stability of the mutated product were normal.