Model for regulator Rh_null caused by two mutations in trans configuration. Of the two mutant copies of RH50 (vertical bars), one contains the 836A mutation and the other carries a defective splice donor in intron 1 (circled a). The RH30 locus is also illustrated whose genomic structure and transcript expression are apparently normal. Diagrammed are the two different levels at which the expression of RH50 is affected (crossed arrows denote blocked steps). The inactive donor is assumed not to alter transcription, but prevents pre-mRNA splicing. This, in turn, leads to degradation of the accumulated hnRNA precursors and no production of mature mRNAs. As a defect likely affecting posttranslational events, E279 (Glu₂₇₉) may disrupt TM9 of Rh50, alter its conformation (indicated by a notch), and impair the interaction with Rh30. As such, the Rh complex could not be assembled in the cell membrane. Changes of the Rh50 mutant in stability or intracellular routing might also contribute to the failure of Rh complex formation.