| First Author | Dycaico MJ | Year | 1988 |
| Journal | Science | Volume | 242 |
| Issue | 4884 | Pages | 1409-12 |
| PubMed ID | 3264419 | Mgi Jnum | J:96771 |
| Mgi Id | MGI:3531398 | Doi | 10.1126/science.3264419 |
| Citation | Dycaico MJ, et al. (1988) Neonatal hepatitis induced by alpha 1-antitrypsin: a transgenic mouse model. Science 242(4884):1409-12 |
| abstractText | 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. |
