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ABSTRACT Air samples of particulate matter (PM) with an aerodynamic diameter less than 10 µm (P[M.sub.10]) were collected from six sites in Bangkok, Thailand, using high-volume air samplers. Daily samples [...]

The Wilms tumor-suppressor gene, WT1, plays a key role in urogenital development, and WT1 dysfunction is implicated in both neoplastic (Wilms tumor, mesothelioma, leukemias, and breast cancer) and nonneoplastic (glomerulosclerosis) disease. The analysis of diseases linked specifically with WT1 mutations, such as Denys-Drash syndrome (DDS), can provide valuable insight concerning the role of WT1 in development and disease. DDS is a rare childhood disease characterized by a nephropathy involving mesangial sclerosis, XY pseudohermaphroditism, and/or Wilms tumor (WT). DDS patients are constitutionally heterozygous for exonic point mutations in WT1, which include mutations predicted to truncate the protein within the C-terminal zinc finger (ZF) region. We report that heterozygosity for a targeted murine Wt1 allele, [Wt1.sup.tmT396], which truncates ZF3 at codon 396, induces mesangial sclerosis characteristic of DDS in adult heterozygous and chimeric mice. Male genital defects also were evident and there was a single case of Wilms tumor in which the transcript of the nontargeted allele showed an exon 9 skipping event, implying a causal link between Wt1 dysfunction and Wilms tumorigenesis in mice. However, the mutant [WT1.sup.tmT396] protein accounted for only 5% of WT1 in both heterozygous embryonic stem cells and the WT. This has implications regarding the mechanism by which the mutant allele exerts its effect.

Gene targeting in embryonic stem cells is employed to generate beta-casein deficient mice to analyze the function of beta-casein in milk. Beta-casein is not required for essential functions and its composition change does not influence the casein micelle. Beta-casein deficiency has an indirect effect on the growth of the pups.

Research using mice with mutant T-cell antigen receptor (TCR) genes shows that rearrangement or expression of the TCR-beta gene is necessary and sufficient for differentiation of CD4-CD8-thymocytes into the CD4+CD8+ form and for expanding the pool of thymocytes. Expression of the TCR-alpha gene is irrelevant to these processes. Furthermore, the TCR-alpha and TCR-beta mutation does not hinder development of gamma and delta T-cells.

A new mouse model for cystic fibrosis (CF) has been devised that should be useful in trials of potential treatments for this deadly autosomal recessive disorder. The new model was produced through mutagenesis or the genetic disruption of the CF transmembrane conductance regulator gene in murine embryonic stem cells. The detection of the characteristic CF pathophysiology in the mice such as abnormal chloride ion transport verified the similarity of the model to human CF.

RB-1, a gene the mutation of which has been linked to retinoblastoma, produces different homozygous and heterozygous effects when inactivated in mouse embryos. Heterozygous mice survive to term and exhibit neither physical abnormalities nor the growth of retinoblastoma tumors. On the other hand, homozygous mouse embryos die before birth and exhibit an array of neural and hematopoietic abnormalities.