AbstractTandTcare dominant mutations in the mouse that affect neuroaxial development when heterozygous and cause embryonic death when homozygous. Embryos were analyzed individually by two‐dimensional gel electrophoresis at 9½ days gestation, 1 day before homozygotes die in utero. A comparison of the protein patterns of mutant homozygotes with those of their littermates revealed a set of proteins (T‐proteins) that showed isoelectric point (pl) polymorphism. All the T‐proteins were more basic in mutant homozygotes. These polymorphisms could be detected, although they were less pronounced, in embryos as young as 7½‐day presomite stages, when it is impossible to distinguish homozygous mutants grossly. Interestingly, the same proteins show a pl shift from basic to acidic in wild‐type embryos during development from 7½ to 9½ days. Thus, it appears that inTandTcmutants a developmentally specific posttranslational acidic modification of these proteins is disturbed. The likely cause of the abnormality is a defect in some mechanism for phosphorylation, since the T‐proteins of wild‐type embryos were shifted to higher pls by phosphatase treatment. This disturbance appears to be localized to axial structures (neural tube, somites, and surrounding mesenchyme) since only these structures, and not the rest of the mutant homozygous embryos, contain abnormally