Tissue Cell Type -Specific Expression

The list of neurons that possess nNOS continues to expand (Vincent and Hope, 1992 Bredt et al., 1991). For example, NO has emerged as a major nonadrenergic noncholinergic transmitter in the enteric nerves (Bult etal., 1990 Desai etal., 1991). In addition to the nervous system, immunore-activity and/or mRNA transcript for nNOS have been detected in skeletal muscle (Nakaneeta/., 1993 Weiner eta/., 1994), pancreatic )8-ceils (Schmidt et al., 1992), the male sex organ (Burnett et al., 1992), the pituitary gland (Wolff and Datto, 1992), the adrenal medulla (Afework et al., 1994 Dun et al., 1993), and the macula densa and distal nephron of the kidneys (Mundel et al., 1992 Terada et al., 1992 Wilcox et al., 1992). Therefore, nNOS is expressed in diverse cell types and tissues. 

The molecular mechanism underlying this diversity in tissue (cell type) expression appears to be alternate promoter usage. Cloning and characterization of nNOS cDNAs from different human tissues have revealed that the S terminus of mRNA molecules is tissue specific. Numerous independent S cDNA ends have been identified in RNA isolated from human brain, skeletal muscle, kidney, and adrenal gland tissue (Marsden et al., 1994a). Some of the 5 cDNA ends are tissue specific, whereas others are more broadly distributed. The 5 ends of mRNA species represent different first 

---

Lindqvist, A., Y. G. He, and S. Andersson. 2005. Cell type-specific expression of beta-carotene 9, 10 -monooxygenase in human tissues. J Histochem Cytochem 53(11) 1403-1412. 

Knittel T, Aurisch S, Neubauet K, et al. Cell-type-specific expression of netrral cell adhesion molecule (N-CAM) in Ito cells of rat liver. Up-regrrlation during in vitro activation and in hepatic tissue repair. Am J Pathol. 1996 149 449-462. 

The value of cultured stem cells to toxicology is in their promise as a continuous source of cells that can be induced to express a chosen cell-type-specific mature phenotype. This achievement would address two current limitations in safety testing scarcity of metabolically competent human systems and use of experimental animals. Numerous culture additives and conditions have been identified that cause commitment and partial differentiation along specific lineages, such as retinoic-acid-induced neuronal commitment of mouse embryonic stem cells. However, definition of conditions that produce fully differentiated cells with cell-type-specific function quantitatively similar to that of intact tissue remains problematic and is a high-priority research area in toxicology. 

In vivo gene expression in animals has been obtained after introduction of DNA encapsulated in liposomes, which are lipid vesicles that entrap the DNA. Further, tissue and cell type specificity has been conferred on the liposomes by coupling to cell-type specific antibodies, resulting in immunoliposom es°. In some cases a combination of liposomes and red blood cell membranes has been used for delivery (Feigner and Rhodes, 1991). 

---