STOCK Rb1^tm3Fad/J

Stock number: 036446
Product name: Rb1^ΔS, Rb1^S
Research areas: Cancer Research, Cell Biology Research

Description

Rb1^ΔS knock-in mice carry an amino acid substitution - F832A - in the Rb1 (RB transcriptional corepressor 1) gene that disrupts interaction with the E2F1 transcription factor. Homozygous mice develop lymphomas (spleen and mesenteric lymph nodes) late in life. These mice may be useful for studying Rb1 and lymphomagenesis.

Detailed description

Rb1(RB transcriptional corepressor 1) functions as a tumor suppressor and is involved in cell cycle regulation. Rb1^ΔS knock-in mice carry an amino acid substitution - F832A - that disrupts interaction with the E2F1 transcription factor and recruitment of EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) to repetitive sequences. Without Rb1 recruitment, EZH2 fails to direct H3K27me3 to silence repetitive sequences resulting in a loss of heterochromatin. Mice homozygous for the mutation are viable and fertile. Expression microarrays of Rb1^ΔS/Rb1^ΔS mouse embryonic fibroblasts (MEFs) demonstrate an increase in repeat sequences. Homozygotes have a median lifespan of 576 days, dying of lymphomas mostly in the spleen and mesenteric lymph nodes. Cell cycle control is not affected by the Rb1^ΔS mutation. These mice may be useful for studying Rb1 in heterochromatin and lymphomagenesis.

Of note: this strain is one of a set of Rb1 and Rbl1 knockins that carry amino acid substitutions that effect binding.
JAX Stock No. 036444 STOCK Rb1^tm1Fad/J Rb1^ΔL
JAX Stock No. 036445 STOCK Rb1^tm2.1Fad/J Rb1^ΔG
JAX Stock No. 036446 STOCK Rb1^tm3Fad/J Rb1^ΔS
JAX Stock No. 036447 STOCK Rbl1^tm1.1Fad/J Rbl1^ΔD

Development

The Rb1^ΔS knock-in allele was created by Dr. Frederick Dick at Western University. The targeting vector was designed to insert an amino acid substitution at position 832 altering phenylalanine to alanine (F832A) in exon 24 of the Rb1 (RB transcriptional corepressor 1) gene on chromosome 14. A loxP-flanked neomycin cassette was placed downstream in intron 24. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were bred to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J mice to remove the neomycin cassette. Progeny were intercrossed and the cre allele removed. 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: Rb1^tm3Fad
Name: targeted mutation 3, Frederick A Dick
MGI accession ID: MGI:5638883
Generation method: Targeted
Attributes: Not Applicable
Synonyms: Rb^deltaS; Rb^S
Marker symbol: Rb1
Marker name: RB transcriptional corepressor 1
Marker synonyms: OSRC; p105-Rb; p110-RB1; pp110; PPP1R130; pRb; Rb; Rb-1; retinoblastoma 1
Chromosome: 14
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A codon change from TTT to GCT introduced the amino acid substitution of alanine for phenylalanine at position 832 (F832A) in exon 24. A loxP-flanked PGK-Neo cassette was inserted downstream of the mutation and was removed via Cre-mediated recombination. This mutation abolishes binding to E2F1.