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To investigate the potential biological role(s) of the PLZF gene, discovered as a fusion with the RARA locus in a patient with acute promyelocytic leukemia harboring a t(11;17) chromosomal translocation, we have isolated its murine homologue (mPLZF) and studied its patterns of developmental expression. The levels of mPLZF mRNAs increased perinatally in the liver, heart, and kidney, but with the exception of the heart, they were either absent or very low in the adult tissues. In situ analysis of mPLZF expression in mouse embryos between 7.0 and 10.5 days of development revealed that mPLZF mRNAs and proteins were coexpressed in spatially restricted and temporally dynamic patterns in the central nervous system. In the hindbrain region, a segmental pattern of expression correlated with the development of the rhombomeres. From 9.0 days of development, starting first in rhombomeres 3 and 5, there was an ordered down-regulation of expression in the center of each rhombomere, so that 1 day later elevated levels of mPLZF mRNAs and proteins were restricted to cells surrounding the rhombomeric boundaries. The chicken homologue of the PLZF gene, which we have also cloned, demonstrated a similar segmental pattern of expression in the hindbrain. To date, PLZF represents the only example of a transcription factor with elevated expression at rhombomeric boundaries. The high degree of evolutionary conservation between the patterns ofPLZF expression during mammalian and avian central nervous system development suggests that it has an important functional role in the regionalization of the vertebrate hindbrain, potentially regulating boundary cell interactions.

Overlapping chromosomal deletions at the albino locus on chromosome 7 of the mouse affect the expression of several liver enzymes, including tyrosine aminotransferase (TAT; L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5). With cloned TAT DNA the integrity of the TAT structural gene and its expression and inducibility by glucocorticoids and cAMP were examined in deletion homozygous mice. No difference in the structure of the gene between normal and mutant mice was detected by Southern blotting. Severely reduced amounts of TAT mRNA were detected in homozygous mutants. The residual mRNA levels could not be modulated by glucocorticoids or cAMP. We conclude that a trans-acting control function required for expression and inducibility of mouse TAT can be assigned to the chromosomal region near the albino locus.The analysis of several overlapping radiation-induced chromosomal deletions at and around the albino locus on chromosome 7 in the mouse has given strong indications for the existence of one or more regulatory factors encoded within the deleted region and concerned specifically with the control of various genes that map on other chromosomes and express liver-specific enzymes and proteins (1).One such enzyme with dramatically reduced activity in deletion homozygous newborn mice is tyrosine aminotransferase (TAT; L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5) (2). The absence of a dosage effect in deletion heterozygotes made it appear unlikely that the lack of enzyme activity was due to the inclusion in the deleted region of the structural gene for TAT. This suspicion was confirmed in subsequent experiments in which somatic cell hybrids between mouse liver cells homozygous for the deletion and hypertetraploid rat hepatoma cells were shown to express normal mouse TAT enzyme activity (3). With the use of an enzyme marker, glucose-6-phosphate isomerase, the TAT structural gene was shown not to map on chromosome 7, which carries the deletion. A similar result was subsequently obtained for glucose-6-phosphatase, also a liver-specific enzyme with virtually no activity in deletion homozygotes but expressed normally in somatic cell hybrids (4). The conclusion was therefore reached that, in individuals homozygous for the deletion in chromosome 7, several liver functions encoded elsewhere in the genome failed to differentiate. Furthermore, the equivalent of the deleted DNA was assumed to include one or more regulatory gene(s) encoding factors essential for the expression of a distinct set of liver-specific functions during the course of differentiation (5).The availability of DNA clones of the rat as well as the mouse TAT gene (refs. 6 and 7; unpublished results) provided the necessary material for attempts to identify the level of this regulatory defect. Therefore, experiments were designed to examine the integrity of the TAT structural gene in deletion homozygous mice as well as the expression and inducibility of this gene by dexamethasone and cAMP. The results of these studies clearly show the TAT...

Livers from newborn mice homozygous for either one of the lethal deletions c14cos or c3H in chromosome 7 have drastically reduced levels of cytosolic phosphoenolpyruvate carboxykinase (GTP) [GTP:oxaloacetate carboxy-lyase