Neonatal Hepatitis Induced by Alpha-1-Antitrypsin - a Transgenic Mouse Model

Dycaico, M. J., Grant, S. G. N., Felts, K., Nichols, W. S., Geller, S. A., Hager, J. H., Pollard, A. J., Kohler, S. W., Short, H. P., Jirik, F. R., Hanahan, D., Sorge, J. A. (December 1988) Neonatal Hepatitis Induced by Alpha-1-Antitrypsin - a Transgenic Mouse Model. Science, 242 (4884). pp. 1409-1412. ISSN 0036-8075

DOI: 10.1126/science.3264419


Transgenic mouse lineages were established that carry the normal (M) or mutant (Z) alleles of the human alpha 1-antitrypsin (alpha 1-Pi) gene. All of the alpha 1-Pi transgenic mice expressed the human protein in the liver, cartilage, gut, kidneys, lymphoid macrophages, and thymus. The human M-allele protein was secreted normally into the serum. However, the human Z-allele protein accumulated in several cell types, but particularly in hepatocytes, and was found in serum in tenfold lower concentrations than the M-allele protein. Mice in one lineage carrying the mutant Z allele expressed high levels of human alpha 1-Pi RNA and displayed significant runting (50% of normal weight) in the neonatal period. This lineage was found to have alpha 1-Pi-induced liver pathology in the neonatal period, concomitant with the accumulation of human Z protein in diastase-resistant cytoplasmic globules that could be revealed in the Periodic acid-Schiff reaction (PAS). The phenotype of mice in the strain expressing high levels of the Z allele is remarkably similar to human neonatal hepatitis, and this strain may prove to be a useful animal model for studying this disease

Item Type: Paper
Subjects: diseases & disorders > cancer > drugs and therapies
organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transgenic animal
CSHL Authors:
Communities: CSHL labs
Depositing User: Gail Sherman
Date: 9 December 1988
Date Deposited: 17 Oct 2017 17:19
Last Modified: 17 Oct 2017 17:19
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