STOCK Rbl1^tm1.1Fad/J

Stock number: 036447
Product name: Rbl1^ΔD, p107^ΔD
Research areas: Cell Biology Research

Description

Rbl1^ΔD knock-in mice carry three amino acid substitutions – I922A, N926A, V930A - in the Rbl1 (RB transcriptional corepressor like 1) gene that interfere with MuvB binding and DREAM complex assembly. These mice may be useful for studying cell cycle regulation and the DREAM complex.

Detailed description

Rbl1 (RB transcriptional corepressor like 1 or p107) encodes a protein similar in sequence and function to RB1 (RB transcriptional corepressor 1). Rbl1 is component of the DREAM complex, which functions in cellular quiescence. The DREAM complex includes an E2F, Rbl1, Rbl2 (p130) and the MuvB core. Rbl1^ΔD knock-in mice carry three amino acid substitutions - I922A, N926A, V930A - that interfere with MuvB binding and DREAM complex assembly. Mice homozygous for the mutation are viable and fertile with no gross phenotype. When combined with B6;129S2-Rbl2^tm1Tyj/J (Stock No. 008176), E18.5 double mutants exhibit defects in chondrocyte proliferation and differentiation, and neonatal lethality. Combining Rbl1^ΔD with B6;129S2-Rbl2^tm2Tyj/J (Stock No. 008177), and 129S.Cg-Ndor1^{Tg(UBC-cre/ERT2)1Ejb}/J (Stock No. 007179) induced loxP recombination in young adult mice and results in a circulatory amyloidosis phenotype caused by ApoAIV overexpression (Perampalam P, et al J Clin Invest 2020). These mice may be useful for studying cell cycle regulation, the DREAM complex, and amyloidosis.

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 Rbl1^ΔD knock-in allele was created by Dr. Frederick Dick at Western University. The targeting vector was designed to insert three amino acid substitutions at position 922 altering isoleucine to alanine (I922A), position 926 altering asparagine to alaninie (N926A), and position 930 altering valine to alanine (V930A) in exon 20 of the Rbl1 (RB transcriptional corepressor like 1) gene on chromosome 2. A loxP-flanked neomycin cassette was place downstream in intron 20. The construct was electroporated into 129S1/Sv-derived CJ7 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: Rbl1^tm1.1Fad
Name: targeted mutation 1.1, Frederick A Dick
MGI accession ID: MGI:5614063
Generation method: Targeted
Attributes: Not Applicable
Synonyms: p107^deltaD; Rbl1^deltaD
Marker symbol: Rbl1
Marker name: RB transcriptional corepressor like 1
Marker synonyms: CP107; p107; pRb1; retinoblastoma-like 1 (p107)
Chromosome: 2
Strain of origin: 129
Molecular note: Exon 20 was replaced with one in which substitutions (I926A, N930A, and V934A) abolished the ability of the product to form the DREAM complex. Cre-mediated recombination removed a floxed neomycin resistance cassette inserted downstream of exon 20.