Abstract

The goal is to investigate the molecular basis of pancreas-specific and parotid-specific gene expression. During the previous grant period, human and mouse amylase genes were cloned and characterized. An amylase minigene which is expressed specifically in pancreas of transgenic mice was constructed. Modifications of this minigene will be used to identify sequences required for transcription in pancreas and parotid. The sequences responsible for response to insulin will also be identified. The tissue-specific expression of ribonuclease phospholipase A2 in parotid and pancreas will be compared with amylase. Trans-acting factors which bind to the tissue-specific regulatory sequences will be purified from nuclear extracts, using an exonuclease protection assay to monitor purification. We will also use a genetic approach to identify tissue-specific regulators, by selection of defective cell lines which lack individual factors. Complementation analysis of these mutants will provide an estimate of the number of factors required for transcription of the pancreatic amylase promoter. The mutant cell lines will be transfected with genomic DNA in order to isolate the genes encoding the tissue-specific regulatory factors. These investigations will contribute to our understanding of the molecular basis of tissue-specific and hormonal regulation of mammalian gene expression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM024872-10A1
Application #
3272595
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1977-06-01
Project End
1991-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
10
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Choy, Christopher H; Saffi, Golam; Gray, Matthew A et al. (2018) Lysosome enlargement during inhibition of the lipid kinase PIKfyve proceeds through lysosome coalescence. J Cell Sci 131:
Stutterd, Chloe; Diakumis, Peter; Bahlo, Melanie et al. (2017) Neuropathology of childhood-onset basal ganglia degeneration caused by mutation of VAC14. Ann Clin Transl Neurol 4:859-864
Lenk, Guy M; Szymanska, Krystyna; Debska-Vielhaber, Grazyna et al. (2016) Biallelic Mutations of VAC14 in Pediatric-Onset Neurological Disease. Am J Hum Genet 99:188-94
Mironova, Yevgeniya A; Lenk, Guy M; Lin, Jing-Ping et al. (2016) PI(3,5)P2 biosynthesis regulates oligodendrocyte differentiation by intrinsic and extrinsic mechanisms. Elife 5:
Lenk, Guy M; Frei, Christen M; Miller, Ashley C et al. (2016) Rescue of neurodegeneration in the Fig4 null mouse by a catalytically inactive FIG4 transgene. Hum Mol Genet 25:340-7
Vaccari, Ilaria; Carbone, Antonietta; Previtali, Stefano Carlo et al. (2015) Loss of Fig4 in both Schwann cells and motor neurons contributes to CMT4J neuropathy. Hum Mol Genet 24:383-96
Lenk, Guy M; Meisler, Miriam H (2014) Mouse models of PI(3,5)P2 deficiency with impaired lysosome function. Methods Enzymol 534:245-60
Menezes, Manoj P; Waddell, Leigh; Lenk, Guy M et al. (2014) Whole exome sequencing identifies three recessive FIG4 mutations in an apparently dominant pedigree with Charcot-Marie-Tooth disease. Neuromuscul Disord 24:666-70
Baulac, Stéphanie; Lenk, Guy M; Dufresnois, Béatrice et al. (2014) Role of the phosphoinositide phosphatase FIG4 gene in familial epilepsy with polymicrogyria. Neurology 82:1068-75
Campeau, Philippe M; Lenk, Guy M; Lu, James T et al. (2013) Yunis-Varón syndrome is caused by mutations in FIG4, encoding a phosphoinositide phosphatase. Am J Hum Genet 92:781-91

Showing the most recent 10 out of 107 publications