Abstract

This research project deals with problems of mammalian developmental genetics. In particular it is concerned with the identification of specific genes, both structural and regulatory, which control various aspects of embryonic development and cell differentiation on levels of morphogenesis and biochemistry. Mutations in the mouse affecting development and differentiation serve as tools in these studies. The identification of genetically caused specific developmental defects provides the potential of elucidating the corresponding normal mechanisms of development and their genetic control. Particular attention centers on a complex of lethal albino deletion in the mouse. These appear to include regulatory genes concerned specifically with the control of liver cell differentiation. Methods of genetics, developmental biology, biochemistry, somatic cell genetics, electronmicroscopy, cytology and molecular biology serve these studies. The research proposed here provides model systems for the study of birth defects and inborn errors of metabolism in humans. It opens up new views on the etiology of congenital malformations and underscores the genetic heterogeneity of conditions with similar appearances, e.g. glycogen storage diseases and other metabolic abnormalities.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM027250-37
Application #
2174904
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1980-04-01
Project End
1995-11-30
Budget Start
1992-04-01
Budget End
1995-11-30
Support Year
37
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Albert Einstein College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Collins, J C; Buchanan, D N; Thoene, J G et al. (1992) Metabolic studies in a mouse model of hepatorenal tyrosinemia: absence of perinatal abnormalities. Biochem Biophys Res Commun 187:340-6
Zaret, K S; Milos, P; Lia, M et al. (1992) Selective loss of a DNase I hypersensitive site upstream of the tyrosine aminotransferase gene in mice homozygous for lethal albino deletions. Proc Natl Acad Sci U S A 89:6540-4
Gluecksohn-Waelsch, S (1992) An overview of developmental genetics in mammals. Curr Opin Genet Dev 2:498-503
Lia, M; Bali, D; Gluecksohn-Waelsch, S (1992) Regulatory genes linked to the albino locus in the mouse confer competence for inducible expression on the structural gene encoding serine dehydratase. Proc Natl Acad Sci U S A 89:2453-5
Gluecksohn-Waelsch, S; DeFranco, D (1991) Lethal chromosomal deletions in the mouse, a model system for the study of development and regulation of postnatal gene expression. Bioessays 13:557-61
DeFranco, D; Bali, D; Torres, R et al. (1991) The glucocorticoid hormone signal transduction pathway in mice homozygous for chromosomal deletions causing failure of cell type-specific inducible gene expression. Proc Natl Acad Sci U S A 88:5607-10
McKnight, S L; Lane, M D; Gluecksohn-Waelsch, S (1989) Is CCAAT/enhancer-binding protein a central regulator of energy metabolism? Genes Dev 3:2021-4
Donner, M E; Leonard, C M; Gluecksohn-Waelsch, S (1988) Developmental regulation of constitutive and inducible expression of hepatocyte-specific genes in the mouse. Proc Natl Acad Sci U S A 85:3049-51
Gluecksohn-Waelsch, S (1986) Developmental genetics of hepatic gluconeogenic enzymes. Ann N Y Acad Sci 478:101-8
Shaw, P A; Adamany, A M (1986) Glycosylation in livers of newborn mice homozygous for a lethal deletion. Proc Soc Exp Biol Med 183:118-24

Showing the most recent 10 out of 12 publications