Nanopore sequencing identifies a distinct Tyr::CreER T2 allele circulating in existing mouse stocks
Year: 2026
Type: preprint
Abstract: ABSTRACT The Tyr::CreER T2 transgenic mouse lines are essential tools for conditional gene manipulation in melanocytes and are widely used in melanoma research. Two independent lines are in common use, the Bosenberg line and the Larue line, with transgene integration sites for both characterised by whole genome sequencing (Aktary et al., 2020). Precise knowledge of these sites is critical for designing complex genetic crosses. Here we report that a Tyr::CreER T2 mouse stock routinely used in Braf CA ;Pten flox melanoma models, and associated with elevated spontaneous melanoma penetrance, carries a previously undescribed integration on Chromosome 1, distinct from the previously reported Chromosome 2 integration. Using long-read Nanopore whole genome sequencing, we mapped the integration to an intergenic locus between Alppl2 and Alpi , revealing a 2,431 bp genomic deletion at the insertion site. We developed position-specific junction PCR and qPCR assays to genotype this allele and confirmed that offspring are born at Mendelian ratios. This distinct integration may account for the elevated melanoma penetrance observed in this stock, with direct implications for the many laboratories employing this widely distributed model. SIGNIFICANCE This study identifies a previously undescribed Tyr::CreER T2 transgene integration on Chromosome 1 in JAX strain 013590, a line widely used across the melanoma research community. Accurate characterisation of this allele has direct practical implications for the many laboratories that rely on this model for studies of melanoma initiation and progression.
Institution: Lancaster University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7171921563