Identified mutations in conserved regions of Jak3, Jak1, and Ikzf3 genes. (A-C, left) Schematic shows the protein domains of Jak3, Jak1, and Aiolos (Ikzf3). Amino acids substitutions caused by single nucleotide variants identified in the WES in samples 853, 854, and 857 are also indicated. FERM indicates a Four-point-one, Ezrin, Radixin, Moesin homology domain. Blue bars represent zinc fingers of Aiolos protein. (A-C; right) Protein sequence alignments comparing Jak1, Jak3, and Aiolos in mouse (Mus musculus), human (Homo sapiens), rat (Rattus norvegicus), African elephant (Loxodonta africana), giant panda (Ailuropoda melanoleuca), Atlantic salmon (Salmo salar), zebrafish (Danio rerio), and tropical frog (Xenopus tropicalis) shows that amino acids that undergo substitution in consequence of a single nucleotide variation are highly conserved between the 2 species. Identical amino acids are marked with an asterisk. (D) Summary of Sanger sequencing screening for the presence of amino acids substitutions in Jak1 (V657F and V655L), Jak3 (T844M and R653H), and Aiolos (R137* and H195T) in a panel of 19 leukemias prepared from Mb1-CreΔPB mice. Filled boxes indicate samples in which mutations were identified by Sanger sequencing.