Taf1 (TATA-box binding protein associated factor 1) encodes the largest subunit of the basal transcription factor TFIID. The Taf1 subunit binds to core promoter sequences in the transcription start site, as well as activators and transcriptional regulators, and participates in the regulation of transcription initiation. Mutations in this gene have been related to X-linked dystonia-parkinsonism (XDP), intellectual disability, and autism spectrum disorder. Specifically, XDP is caused by insertion of a SINE-VNTR-Alu (SVA) subfamily F retrotransposon into intron 32 of the human TAF1 gene on the X chromosome. The SVA_F retrotransposon contains a (CCCTCT)n hexanucleotide repeat tract of variable length, which is inversely correlated with age at disease onset and disease severity in human patients. Taf1PCdeltaSVA knock-in (KI) mice harbor one loxP site in intron 24 of the endogenous mouse Taf1 gene. Additionally, a marker cassette was inserted 6.5 kb downstream of the mouse Taf1 gene. This marker cassette includes mNeonGreen, human HPRT1 and NeoR genes, all driven by the human eukaryotic translation elongation factor 1 alpha 1 EEF1A1 promoter, and terminated by the SV40 polyadenylation sequence, followed by a second loxP site. These Taf1PCdeltaSVA KI mice also harbor a partial human TAF1 gene sequence, derived from an XDP patient, spanning from intron 24 (2654 bp of this intron) through 7.6 kb downstream of the 3' UTR. The XDP-causing SVA_F retrotransposon has been precisely removed from this construct which is otherwise identical to the Taf1PC-XDP mouse line (<a href="https://www.jax.org/strain/003771">RRID:MMRRC_075973-JAX</a>). The human TAF1 portion includes other genetic variants that are part of the XDP haplotype. Of note, the human TAF1 exons have been engineered to code for a mouse TAF1 protein by substituting a total of 18 amino acids (AAs) and deleting two AAs. Prior to Cre-mediated recombination, these Taf1PCdeltaSVA mice express wild-type mouse TAF1 protein and green fluorescent protein as well as human HPRT1 and a NeoR selectable marker. When bred to a tissue-specific Cre recombinase strain, recombination occurs between the loxP site in mouse Taf1 intron 24 and the second loxP site that precedes the human TAF1 intron 24, resulting in expression of a fusion of mouse Taf1 exons 1-24 with human TAF1 exons 25-38, in cre-expressing tissues. Homozygous Taf1PCdeltaSVA knock-in females and hemizygous Taf1PCdeltaSVA males are viable and fertile, with no overt phenotype. The donating laboratory crossed these Taf1PCdeltaSVA KI mice to a Nestin-Cre mouse line (<a href="https://www.jax.org/strain/003771">RRID:IMSR_JAX:003771</a>) and resulting progeny demonstrated normal phenotypes. The donating investigator notes that although Taf1PCdeltaSVA ESCs are visibly green under UV light, GFP expression has not been evaluated by either direct fluorescence or by immunohistochemistry methods in the mouse tissues. Whereas the Taf1PC-XDP KI mice may be useful for studying X-linked dystonia-parkinsonism, these Taf1PCdeltaSVA mice serve as ideal negative controls for such studies.

The use of this mouse model is subject to the terms and conditions of the Limited Use Label License from Caribou Biosciences, Inc.

The use of this mouse strain or other product (the "Licensed Product") is subject to the terms and conditions of the Limited License from The Broad Institute.

Use of MICE by companies or for-profit entities requires a no-fee JAX Leap License prior to shipping.

Taf1PCdeltaSVA knock-in (KI) mice harbor a loxP site in intron 24 of the endogenous Taf1 locus, a marker cassette that includes mNeonGreen sequence, driven by a human EEF1A1 promoter, and a second loxP site followed by human TAF1 gene sequence from intron 24 through the 3' UTR. Prior to Cre-mediated recombination, these Taf1PC-XDP mice will express wildtype mouse TAF1 protein, green fluorescent protein as well as human HPRT1 and a NeoR selectable marker. When bred to a tissue-specific Cre recombinase strain, resulting offspring will express a fusion of mouse Taf1 exons 1-24 with human TAF1 exons 25-38, in cre-expressing tissues. These mice may be useful as a control strain to the Taf1PC-XDP KI mouse line (<a href="https://www.jax.org/strain/003771">RRID:MMRRC_075973-JAX</a>) when studying X-linked dystonia-parkinsonism.

This strain is hosted by NIH's MMRRC, which partners with JAX for the distribution of this and other strains. For additional information and to purchase, please visit the MMRRC site.