Hnrnpa1 Conditional Knockout mouse models

Hnrnpa1, the mouse ortholog of human HNRNPA1, encodes heterogeneous nuclear ribonucleoprotein A1, an abundant RNA-binding protein with tandem RRM domains and a carboxy-terminal low-complexity prion-like domain that drives reversible liquid-liquid phase separation. A1 antagonizes SR proteins to control alternative splice site selection, participates in mRNA export and internal ribosome entry site-dependent translation, and shuttles through the M9 signal recognized by transportin-1. Disease mutations in the prion-like domain, notably D262V, accelerate fibrillization and cause multisystem proteinopathy with inclusion body myopathy, Paget disease of bone, and ALS, so knockin alleles preserve the gain-of-toxic-assembly mechanism that deletion cannot reproduce. Because A1 is broadly required for splicing homeostasis, conditional floxed alleles paired with neuron- or muscle-restricted Cre drivers are safer than germline deletion for adult phenotyping. The paralog Hnrnpa1l2 and the related Hnrnpa2b1 overlap substantially in target repertoire, so score splicing outcomes transcriptome-wide instead of assuming loss produces a clean null state.

Conditional deletion of Hnrnpa1 limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to Hnrnpa1 floxed stock yields usable cohorts.