1. Salivary protein genetic polymorphisms. The long term objective is to better understand the mutation mechanisms that produce such an abundant variety of polymorphic forms in the saliva.
The specific aim i s to biochemically characterize mutant forms of proline-rich and histatin proteins by cloning and sequencing the genomic DNA of specific alleles at PRP and His loci. It is possible that genetic variation of salivary proteins, by altering the oral microenvironment, may relate to different disease susceptibilities among individuals. 2. Cell culture of Macaque and human salivary gland epithelia. The long term objective is to determine the intra and extracellular factors that regulate the expression of salivary-type genes coding for proline-rich proteins (PRPs), histatins, statherin and cystatins. These studies would be greatly enhanced by the availability of transformed salivary gland epithelial cell lines.
The specific aim i s to determine the conditions for primary cell culture of Macaque and human salivary gland epithelial cells and to transform them in order to establish permanent cell lines that express salivary-type genes. Perhaps this may lead to a better understanding of salivary-type gene regulation, and the principles so- derived might be used to manipulate and favorably alter the oral microenvironment in ways conductive to oral health. 3. Application of molecular techniques to the study of taste transduction in the mouse. The long term objective is to better understand the molecular basis of taste transduction. We have two specific aims: a. To prove directly by transgenic mouse experiments the role of salivary and von Ebner's gland secreted PRPs in the perception of bitter taste. Such a role is strongly supported by previous genetic evidence. b. To establish a taste cell-specific cDNA library in the mouse as an important resource in identifying molecules that play a role in transducing taste. These studies may increase understanding of the relationships between the chemical senses and the oral environment.
|Neira, M; Danilova, V; Hellekant, G et al. (2001) A new gene (rmSTG) specific for taste buds is found by laser capture microdissection. Mamm Genome 12:60-6|
|Harder, D B; Azen, E A; Whitney, G (2000) Sucrose octaacetate avoidance in nontaster mice is not enhanced by two type-A Prp transgenes from taster mice. Chem Senses 25:39-45|
|Sabatini, L M; Azen, E A (1994) Two coding change mutations in the HIS2(2) allele characterize the salivary histatin 3-2 protein variant. Hum Mutat 4:12-9|
|Sabatini, L M; Ota, T; Azen, E A (1993) Nucleotide sequence analysis of the human salivary protein genes HIS1 and HIS2, and evolution of the STATH/HIS gene family. Mol Biol Evol 10:497-511|
|Azen, E A (1993) Genetics of salivary protein polymorphisms. Crit Rev Oral Biol Med 4:479-85|
|Azen, E A; Latreille, P; Niece, R L (1993) PRBI gene variants coding for length and null polymorphisms among human salivary Ps, PmF, PmS, and Pe proline-rich proteins (PRPs). Am J Hum Genet 53:264-78|
|Azen, E; Prakobphol, A; Fisher, S J (1993) PRB3 null mutations result in absence of the proline-rich glycoprotein Gl and abolish Fusobacterium nucleatum interactions with saliva in vitro. Infect Immun 61:4434-9|
|Capeless, C G; Whitney, G; Azen, E A (1992) Chromosome mapping of Soa, a gene influencing gustatory sensitivity to sucrose octaacetate in mice. Behav Genet 22:655-63|
|Azen, E A; O'Connell, P; Kim, H S (1992) PRB2/1 fusion gene: a product of unequal and homologous crossing-over between proline-rich protein (PRP) genes PRB1 and PRB2. Am J Hum Genet 50:842-51|
|Sabatini, L M; Allen-Hoffmann, B L; Warner, T F et al. (1991) Serial cultivation of epithelial cells from human and macaque salivary glands. In Vitro Cell Dev Biol 27A:939-48|
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