We report that keratin 8 (inK8) gene disruption causes colorectal hyperplasia in FVB/N mice. The intestinal lesions affect uniformly the cecum, colon, and rectum but not the small intestine. The elongation of the crypts is accompanied by an inflammation of the lamina propria and submucosa. Hepatic, renal, and pancreatic functions tested in clinical assays are within nonpathological range, suggesting that the major defect lies in colonic epithelial cells. Still, small but consistent elevation in the hepatic enzymes alanine (AST) and asparate (ALT) aminotransferase are observed, along with a 70% increase in spleen weight. No homozygous mouse line has been established, because of a markedly reduced fertility of the mK8 -/-females. Previously, we reported that the inKS-targeted mutation causes embryonic lethality in (C57BI/6x 129Sv} mice. This strong effect of the genetic background on the inK8-mutant phenotype emphasizes the importance of using several inbred mouse strains to reveal the polygenic contribution to mutant phenotypes. Our results demonstrate that genetic modifiers of K8/K18 filament functions, with profound effects on embryogenesis and gut functional integrity, are differentially active in the FVB/N and C57B1/6 genetic backgrounds. More importantly, the increase in inKS-/-gut epithelial cell number, rather than cell disruption, contrasts with the known function of epidermal keratins in providing mechanical strength.

Carbon nanotubes are an intriguing new form of carbon, comprising molecular-scale cylinders of nanometer diameter and micrometer to centimeter lengths. They exhibit many extraordinary mechanical and electrical properties and have a wide variety of anticipated applications. However, to realize these potential applications, chemists need to develop means by which to manipulate these nanotubes in a predictable and controllable way. Novel sidewall-modified carbon nanotubes functionalized with polymers, such as poly(methyl methacrylate) (PMMA), have been prepared to gain control over the properties of nanocomposites on the molecular level. Characterization of these materials has been limited by their insolubility in organic solvents. Here the interaction between the carbon nanotube and the polymer has been studied through the use of solid-state nuclear magnetic resonance (NMR) and scanning tunneling microscopy (STM). Fast magic-angle spinning (30 kHz), to achieve high-resolution 1H NMR, together with advanced pulse sequences such as 1H double quantum NMR with the BABA (back-to-back) sequence, and heteronuclear 1H−13C sequences, are used to demonstrate the association of the initiator moieties and polymers with the surface of the nanotubes. The findings are supported by STM data of nanotubes before and after functionalization with the initiator groups.

Keratin 8 and 18 are commonly used as tumorigenic markers for various types of carcinomas. They are known to be involved in cell migration, cell invasiveness, plasminogen activity and drug and radiation resistance. To ascertain a potential function for simple epithelium keratins in mammary adenocarcinoma in vivo, keratin-8-deficient mice (mK8) were mated with transgenic mice carrying the middle T oncogene driven by the MMTV promoter. The resulting mK8 knockout and control progeny carrying the middle T transgene developed mammary gland tumours with the same incidence. However, the onset of palpable mammary gland tumours occurred earlier in mK8 mutant than in control mice. This effect was prominent in males where the onset in control animals is delayed overall, because of the lower hormonal inducibility of the MMTV promoter. Metastatic foci were observed in the lungs of all females and of a few males, independently of the genotype. Histological analysis revealed no morphological differences of the tumorigenic cells in primary tumours nor in metastatic foci. As expected, keratin 8 was absent in the mK8 tumours. Keratin 7 (mK7), keratin 18 (mK18) and keratin 19 (mK19) protein were observed in both primary and metastatic foci. These results constitute the first in vivo analysis of the role of simple epithelium keratins in mammary carcinogenesis. It demonstrates that the latency, but not the incidence nor the morphological features, of PyV middle T-induced mammary gland tumours is affected by keratin 8 deficiency.

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