Frequency, junctional characteristics, and clonality of illegitimate V(D)J recombination events in Notch1 and Bcl11b genes during mouse development

Illegitimate V(D)J recombination of oncogenes and tumor suppressor genes is implicated in the formation of several T cell malignancies. Notch1 and Bcl11b are genes involved in T cell development, selection, proliferation, and survival that contain hotspots for deletional illegitimate V(D)J recombination.;This study analyzed the frequency and junctional processing of Notch1 and Bcl11b deletions during mouse development. Results show deletions resemble authentic V(D)J recombination at the T cell receptor beta (TCRβ) loci, contrasting with deletions observed in the human, non-immune HPRT1 gene.;Deletions are detected in thymic and splenic T cell populations. In thymus, deletions increase in frequency between fetal and postnatal stages, are detected in older animals, exhibit limited clonality, and are more frequent in Bcl11b..;Deletion junctions in Bcl11b exhibit greater germline nucleotide loss, while in Notch1, palindromic nucleotides are more abundant. Non-templated nucleotide insertions increase between fetal and juvenile stages, and nucleotide compositions are consistent with normal terminal deoxynucleotidyl transferase (TdT) activity.