Thomas Gridley

Hoxa-2 mutant mice exhibit homeotic transformation of skeletal elements derived from cranial neural crest

Mice homozygous for a targeted mutation of the Hoxa-2 (Hox 1.11) gene are born with cleft palates and die within 24 hr of birth. Analysis of stained skeletons revealed that homozygous mutant animals contained multiple cranial skeletal defects, including a duplication of the ossification centers of the bones of the middle ear. Histological analysis suggested that this duplication resulted from the transformation of skeletal elements derived from the second branchial arch into more anterior structures, resulting in a duplication of Meckels cartilage adjacent to the otic capsule. Skeletal elements normally derived from the second arch were absent in the mutants. These data provide direct experimental evidence for the existence of a branchial Hox code.

Notch Activity Influences the αβ versus γδ T Cell Lineage Decision

Abstract The choice between the αβ or γδ T cell fates is influenced by the production of functional, in-frame rearrangements of the TCR genes, but the mechanism that controls the lineage choice is not known. Here, we show that T cells that are heterozygous for a mutation of the Notch1 gene are more likely to develop as γδ T cells than as αβ T cells, implying that reduced Notch activity favors the γδ T cell fate over the αβ T cell fate. A constitutively activated form of Notch produces a reciprocal phenotype and induces thymocytes that have functional γδTCR gene rearrangements to adopt the αβ T cell fate. Our data indicate that Notch acts together with the newly formed T cell antigen receptor to direct the αβ versus γδ T cell lineage decision.

Mice homozygous for a null mutation of activin βB are viable and fertile

Abstract We have made a null mutation in the mouse activin β B gene by deleting the portion of the gene encoding the proteolytic cleavage site and the majority of the coding region for the mature processed protein. Mice homozygous for this mutation complete embryogenesis and are completely viable. Approximately 40% of the homozygous mutant animals are born with open eyes. Aside from the incompletely penetrant eye defects, histopathological analysis has not revealed any other abnormalities in homozygous mutant animals. Breeding tests have shown that both male and female homozygous mutant animals are fertile.

Cloning and developmental expression of Grg, a mouse gene related to the groucho transcript of the Drosophila Enhancer of split complex

Genes of the Enhancer of split complex are involved in neural-epidermal cell fate decisions during early embryogenesis in Drosophila. One of these genes, the product of the Enhancer of split m9/10 or groucho transcript, encodes a ubiquitous nuclear protein with homology at the carboxy-terminus to G-protein beta-subunits. Here we describe the cloning and RNA expression analysis of a mouse gene, designated Grg, that is homologous to just the amino-terminal region of the groucho product. Grg encodes a 197 amino acid protein that shares 53% amino acid identity with the corresponding region of the product of the Drosophila groucho gene. However, the mouse Grg protein does not contain the region homologous to G-protein beta-subunits. An analysis by in situ hybridization of the spatial and temporal localization of Grg RNA expression revealed that, while the initial pattern of Grg expression was quite restricted, by midgestation Grg RNA was ubiquitously expressed in the developing embryo. Widespread Grg RNA expression was maintained in adult mice. The implications of these results for the existence of separable functional domains of the Drosophila groucho product, and possible roles of the Grg gene during mouse development, are discussed.

Cloning, sequencing and expression of the mouse mammalian achaete-scute homolog 1 (MASH1).

We describe the cloning of a full length cDNA encoding the mouse mammalian achaete-scute homolog 1 (mouse MASH1). Using a ribonuclease protection assay to examine expression of this gene in cell lines, postimplantation embryos and adult tissues, expression was detected between days 10.5 and 16.5 of gestation and in adult brain. No expression was detected in other adult tissues or in most of the cell lines examined. However, differentiation of P19 embryonal carcinoma cells into neuronal cell types by exposure to retinoic acid resulted in the induction of MASH1 RNA expression.