FVB(129P2)-Pde6b⁺ Gtf2ird1^em3Jdd Tyr^c-ch/Mmjax

Stock number: 034672
Product name: Gtf2ird1^em1bpins
Research areas: Cell Biology Research, Dermatology Research, Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research, Sensorineural Research

Description

Gtf2ird1 (general transcription factor II I repeat domain-containing 1)knock-out mice carry a CRISPR/Cas9-mediated 1 bp insertion in exon 3. Homozygous KO mice exhibit altered skull morphology and alterations in behavior. This strain may be useful for studying Williams-Beuren syndrome, a developmental disorder characterized by the deletion of the 28 genes of the Williams syndrome critical region.

Detailed description

Gtf2ird1 (general transcription factor II I repeat domain-containing 1) encodes a protein that functions as a regulator of transcription and is located on the telomeric end of the 28 gene Williams syndrome critical region (WSCR). Mutations in Gtf2ird1 are associated with some of the physical, cognitive, and behavioural phenotypes found in Williams-Beuren syndrome (a deletion of the WSCR). Gtf2ird1 knock-out (KO) mice carry a CRISPR/Cas9-mediated 1 bp adenine insertion in exon 3 that results in a non-functional N-terminal truncation of the GTF2IRD1 protein. The strain is maintained on a "sighted" FVB/N background. Mice homozygous for Gtf2ird1 are viable and exhibit several behavioral abnormalities including: a decrease in balance, decreased marble burying, and enhanced fear conditioning. This strain may be useful for studying Williams-Beuren syndrome.

Development

CRISPR/cas9 endonuclease-mediated genome editing was used to create a 1 bp adenine insertion in exon 3 of the Gtf2ird1 gene. The deletion causes a frameshift mutation that introduces a premature stop codon. The resulting N-truncated protein has diminished binding capacity. There is a 40% reduction of protein in homozygotes. Single guide RNA and Cas9 endonuclease were introduced into FVB/N-derived fertilized eggs by pronuclear injection. Embryos were transferred to pseudopregnant females, and correctly targeted pups were bred to FVB.129P2-Pde6b⁺ Tyr^c-ch/AntJ (sighted FVB) mice for germline transmission. The colony was maintained on the FVB.129P2-Pde6b⁺ Tyr^c-ch/AntJ background. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize FVB.129P2-Pde6b⁺ Tyr^c-ch/AntJ oocytes.

Allele

Symbol: Gtf2ird1^em3Jdd
Name: endonuclease-mediated mutation 3, Joseph D Dougherty
MGI accession ID: MGI:6429892
Generation method: Endonuclease-mediated
Attributes: Hypomorph
Synonyms: Gtf2ird1^em1bpins
Marker symbol: Gtf2ird1
Marker name: general transcription factor II I repeat domain-containing 1
Marker synonyms: BEN; binding factor for early enhancer; Cream1; ESTM9; Gtf3; hMusTRD1alpha1; MUSTRD1; RBAP2; WBS; WBSCR11; WBSCR12
Chromosome: 5
Strain of origin: FVB/N
Molecular note: CRISPR/cas9 endonuclease-mediated genome editing was used to create a 1 bp adenine insertion in exon 3 of the gene. The deletion causes a frameshift mutation that introduces a premature stop codon. The resulting N-truncated protein has diminished binding capacity. There is a 40% reduction of protein in homozygotes.

Allele

Symbol: Pde6b⁺
Name: wild type
MGI accession ID: MGI:2430003
Generation method: Not Applicable
Marker symbol: Pde6b
Marker name: phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide
Marker synonyms: CSNB3; CSNBAD2; GMP-PDEbeta; nmf137; PDEB; r; rd; rd1; rd10; RP40
Chromosome: 5
Strain of origin: Not Applicable
Expressed genes: Pde6b,phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide,mouse, laboratory
Site of expression: Retina.

Allele

Symbol: Tyr^c-ch
Name: chinchilla
MGI accession ID: MGI:1855977
Generation method: Spontaneous
Synonyms: c^ch; c^r
Marker symbol: Tyr
Marker name: tyrosinase
Marker synonyms: ATN; CMM8; Oca1; OCA1A; OCAIA; SHEP3; skc35
Chromosome: 7
Strain of origin: fancier's stock
Molecular note: The mutation in the chinchilla allele was found to be a G-to-A point mutation that results in an amino acid change at position 482 or 464 from alanine to threonine (p.A482T for pre-protein, p.A464T for mature protein).