A foreign beta-globin gene in transgenic mice: integration at abnormal chromosomal positions and expression in inappropriate tissues.

We have investigated the chromosomal location, inheritance, and expression of a cloned rabbit beta-globin gene introduced into the mouse germ line by microinjection into mouse eggs. Experiments utilizing in situ hybridization to metaphase chromosomes show that the gene has integrated into one or two different chromosomal loci in each of five mouse lines analyzed. Each locus contains between three and forty copies of the foreign DNA sequence arranged in a tandem array, and the sequences at each locus are stably inherited as a single Mendelian marker. Neither globin mRNA nor polypeptides encoded by the rabbit beta-globin gene are detected in erythroid cells in the seven transgenic lines examined, indicating that the expression of the foreign gene is not correctly regulated. However, in two of the mouse lines, rabbit beta-globin transcripts are found at a low level in specific, although inappropriate, tissues: skeletal muscle in one line and testis in another line. These unusual patterns of beta-globin gene transcription are heritable traits in the two mouse lines and may result from the beta-globin gene's integration at abnormal chromosomal positions.