Simple theoretical criterion of chemical carcinogenicity - a refutation.

The quasi-valence number criterion for chemical carcinogenicity has been shown, through several examples, to be untenable.     

Congenital heart disease in mice deficient for the DiGeorge syndrome region.

The heterozygous chromosome deletion within the band 22q11 (del22q11) is an important cause of congenital cardiovascular defects. It is the genetic basis of DiGeorge syndrome and causes the most common deletion syndrome in humans. Because the deleted region is largely conserved in the mouse, we were able to engineer a chromosome deletion (Df1) spanning a segment of the murine region homologous to the human deleted region. Here we describe heterozygously deleted (Df1/+) mice with cardiovascular abnormalities of the same type as those associated with del22q11; we have traced the embryological origin of these abnormalities to defective development of the fourth pharyngeal arch arteries. Genetic complementation of the deletion using a chromosome duplicated for the Df1 DNA segment corrects the heart defects, indicating that they are caused by reduced dosage of genes located within Df1. The Df1/+ mouse model reveals the pathogenic basis of the most clinically severe aspect of DiGeorge syndrome and uncovers a new mechanism leading to aortic arch abnormalities. These mutants represent a mouse model of a human deletion syndrome generated by chromosome engineering.     

Intramuscular comparison of myosin isozymes and light chains in rat extensor digitorum longus muscle

Complete muscle cross sections were obtained from the proximal and distal third regions of ten rat extensor digitorum longus muscles. Electrophoretic methods were then used to quantify the various myosin isozymes and light chains in each muscle specimen. The results demonstrated that the relative distribution of the various myosin isozyme and light chain variables do not vary significantly between the two sampling regions.     

Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type

Methylmalonic aciduria and homocystinuria, cblC type (OMIM 277400), is the most common inborn error of vitamin B(12) (cobalamin) metabolism, with about 250 known cases. Affected individuals have developmental, hematological, neurological, metabolic, ophthalmologic and dermatologic clinical findings. Although considered a disease of infancy or childhood, some individuals develop symptoms in adulthood. The cblC locus was mapped to chromosome region 1p by linkage analysis. We refined the chromosomal interval using homozygosity mapping and haplotype analyses and identified the MMACHC gene. In 204 individuals, 42 different mutations were identified, many consistent with a loss of function of the protein product. One mutation, 271dupA, accounted for 40% of all disease alleles. Transduction of wild-type MMACHC into immortalized cblC fibroblast cell lines corrected the cellular phenotype. Molecular modeling predicts that the C-terminal region of the gene product folds similarly to TonB, a bacterial protein involved in energy transduction for cobalamin uptake.     

Simple theoretical criterion of chemical carcinogenicity—a refutation

Summary The quasi-valence number criterion for chemical carcinogenicity has been shown, through several examples, to be untenable.     

A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2.

We recently described a disorder termed Huntington disease-like 2 (HDL2) that completely segregates with an unidentified CAG/CTG expansion in a large pedigree (W). We now report the cloning of this expansion and its localization to a variably spliced exon of JPH3 (encoding junctophilin-3), a gene involved in the formation of junctional membrane structures.