Know Your Neighbors: Three Phenotypes in Null Mutants of the Myogenic bHLH Gene MRF4

Abstract

skeletal muscle and skeletal muscle precursors, and on cell culture experiments, all of which pointed to func-and B. J. Wold § *Hamon Center for Basic Cancer Research tions in specification of myoblasts and execution of muscle differentiation. The major muscle phenotypes The University of Texas Southwestern Medical Center at Dallas described thus far are the failure of muscle differentiation in mice homozygous for myogenin null mutations Dallas, Texas 75235-9148 † Technische Universitat Braunschweig (Hasty et al., 1993; Nabeshima et al., 1993) and failure to produce the myogenic precursor cell population in Institut fur Biochemie und Biotechnologie 3300 Braunschweig mice deficient in both MyoD and Myf5 (Rudnicki et al., 1993). Unlike muscle deficits, the skeletal phenotypes Federal Republic of Germany ‡ Division of Eukaryotic Molecular Genetics were not expected, although they can account for the lethality of several MRF mutations. MRC National Institute for Medical Research London NW7 1AA MRF4 (Rhodes and Konieczny, 1989) is the final myogenic bHLH gene to be targeted in mice. It is located United Kingdom § Division of Biology 156-29 approximately 8 kb 5Ј of Myf5 on mouse chromosome 10. The proximity of MRF4 and Myf5 to each other raises

Role of a locus control region in the mutually exclusive expression of human red and green cone pigment genes

“…Cre-mediated excision of the 3Ј-flanking PGK-neo gene produced changes of up to several-fold in the frequency of reporter-gene expression, the largest effect being seen in line pPMS107 1E2, in which the frequency of AP-only cells declined 3-fold, and the frequencies of lacZ-only and APϩlacZ cells increased 2.5-and 3-fold, respectively. Overall, the effect of the PGK-neo selectable marker seems to be smaller in this setting than in some of the experimental arrangements reported by others (10)(11)(12).…”

The Role of PKD in Cell Polarity, Biosynthetic Pathways, and Organelle/F-actin Distribution

“…Concerning differences between the phenotype of the KO mice in this paper and those of the preceding papers, we consider it may be due to a difference in the structure of the targeting vectors because similar discrepancies were reported several times in the past (Ohno et al, 1994;Olson et al, 1996). In these cases, a difference in the position or direction of the promoter and drug resistance gene was reported to affect the expression or splicing of neighboring genes.…”

Targeting genes for self-excision in the germ line

“…Limitations imposed by the transformation and recombination efficiencies of mammalian cells require that the alteration of interest be linked physically to a selectable genetic marker, typically a gene encoding drug resistance under transcriptional control of a constitutive promoter/enhancer element. This operational requirement can have unpredictable consequences in vivo, such as misregulation of adjacent genes (Olson et al 1996) or the attenuation of expression of the gene of interest (Colledge et al 1995;Meyers et al 1998). Thus, the elimination of the marker may be desirable and, for technical reasons, is generally performed through use of site-specific recombinase systems such as Cre/loxP (Sternberg and Hamilton 1981) or FLP/FRT (Broach and Hicks 1980).…”