ULTRASTRUCTURAL BASIS OF BIOCHEMICAL EFFECTS IN A SERIES OF LETHAL ALLELES IN THE MOUSE : Neonatal and Developmental Studies

The fine structure of newborn and fetal mouse liver and of newborn kidney cells homozygous for any of three albino alleles known to have multiple biochemical effects was investigated. Electron microscope studies of mutant cells revealed dilation and vesiculation of the rough endoplasmic reticulum in parenchymal liver cells, as well as dilation and other anomalies of the Golgi apparatus. These abnormalities were observed in all newborn mutants but never in littermate controls. Although they were most pronounced in liver parenchymal cells, they were found also to a lesser degree in kidney cells, but they were absent altogether in other cell types of the mutant newborn. Homozygous fetuses showed similar anomalies in the liver at 19 days of gestational age. In one of the alleles studied, mutant liver parenchymal cells were found to be abnormal as early as the 18th day of gestation. There appears to be a striking parallelism between the biochemical defects and those of the cellular membranes in homozygous mutant newborn and fetuses. Although the specific nature of the mutational effect on membrane structure remains unknown, the results are compatible with the assumption that a mutationally caused defect in a membrane component interferes with a mechanism vital in the integration of morphological and biochemical differentiation

Two Genetically Defined Tram-Acting Loci Coordinately Regulate Overlapping Sets of Liver-Specific Genes

Mice homozygous for deletions around the albino locus fail to activate expression of a set of neonatal liver functions and die shortly after birth. This phenotype is thought to result from the loss of a positive trans-acting factor, denoted alf, in deletion homozygotes. Using differential cDNA screening, we isolated and characterized genes whose cell type-specific transcription is affected by alf and found as a common feature that expression of these genes is induced by glucocorticoids and cAMP. Surprisingly, a subset of these alf-responsive genes is negatively controlled by the tissue-specific extinguisher locus Tse-1. Administration of glucocorticoids and cAMP leads to reversal of Tse-1—mediated extinction of these genes. These results show that two trans-acting factors coordinately regulate expression of overlapping sets of liver-specific genes. We suggest that both the lethal phenotype and the extinguished state result from interference with hormone signal transduction

Cooperativity of Glucocorticoid Response Elements Located Far Upstream of the Tyrosine Aminotransferase Gene

Two glucocorticoid response elements (GREs) located 2.5 kb upstream of the transcription initiation site of the tyrosine aminotransferase gene were identified by gene transfer experiments and shown to bind to purified glucocorticoid receptor. Although the proximal GRE has no inherent capacity by itself to stimulate transcription, when present in conjunction with the distal GRE, this element synergistically enhances glucocorticoid induction of gene expression. Cooperativity of the two GREs is maintained when they are transposed upstream of a heterologous promoter. An oligonucleotide of 22 bp representing the distal GRE is sufficient to confer glucocorticoid inducibility. As evidenced by the mapping of DNAase I hypersensitive sites, local alterations in the structure of chromatin at the GREs take place as a consequence of hormonal treatment

Post-meiotic transcription in mouse testes detected with spermatid cDNA clones

cDNA clones to poly(A) + mRNA from spermatids have been obtained to study gene transcription in post-meiotic germ cells. Four cDNA clones detect mRNAs that increase in abundance in post-meiotic germ cells. One clone, pPM459, was shown to correspond to an mRNA that is transcribed after meiosis. Pulse-labelling experiments demonstrate transcription o5 the message in spermatids. These data constitute further evidence for post-meiotic gene transcription in spermatids.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44190/1/10540_2005_Article_BF01116696.pd