+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Neonatal hepatitis induced by alpha 1-antitrypsin: a transgenic mouse model

Neonatal hepatitis induced by alpha 1-antitrypsin: a transgenic mouse model

Science 242(4884): 1409-1412

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.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 040780924

Download citation: RISBibTeXText

PMID: 3264419

DOI: 10.1126/science.3264419

Related references

Histopathology of alpha 1-antitrypsin liver disease in a transgenic mouse model. Hepatology 12(1): 40-47, 1990

Histopathology of alpha 1 antitrypsin a1at liver disease in a transgenic mouse model. Laboratory Investigation 60(1): 33A, 1989

Evaluation of a transgenic mouse model for alpha-1-antitrypsin (AAT) related liver disease. Annals of Human Genetics 58(4): 305-320, 1994

Dysplasia and hepatocellular carcinoma in a transgenic mouse model for alpha 1 antitrypsin liver disease. Laboratory Investigation 62(1): 36A, 1990

Spontaneous development of dysplasia nodules adenomas and hepatocellular carcinoma in a transgenic mouse model for alpha 1 antitrypsin deficiency. Laboratory Investigation 64(1): 91A, 1991

Alpha 1 antitrypsin deficiency as a cause of neonatal hepatitis. Pediatria Polska 61(12): 808-813, 1986

Alpha-1-antitrypsin MZ phenotype A cause of neonatal hepatitis. Gastroenterology 112(4 Suppl. ): A914, 1997

Serum alpha-fetoprotein levels in extrahepatic biliary atresia, idiopathic neonatal hepatitis and alpha-1-antitrypsin deficiency (PiZ). Acta Paediatrica Scandinavica 65(5): 623-629, 1976

Alpha-1 Antitrypsin Gene Therapy Ameliorates Bone Loss in Ovariectomy-Induced Osteoporosis Mouse Model. Human Gene Therapy 27(9): 679-686, 2016

Concentration and activity of alpha-1-antitrypsin in neonatal hepatitis. Boletin Medico del Hospital Infantil de Mexico 35(4): 617-623, 1978

Modification of the alpha 1-antitrypsin phenotype in neonatal hepatitis. Archives of Disease in Childhood 60(4): 378-379, 1985

Elevated synthesis of human alpha 1-antitrypsin hinders the secretion of murine alpha 1-antitrypsin from hepatocytes of transgenic mice. Journal of Biological Chemistry 264(26): 15696-15700, 1989

Neonatal hepatitis and alpha-1-antitrypsin deficiency. The prognosis in five patients. Mayo Clinic Proceedings 52(4): 241-245, 1977

Hepatocarcinogenesis is the sequel to hepatitis in Z#2 alpha 1-antitrypsin transgenic mice: histopathological and DNA ploidy studies. Hepatology 19(2): 389-397, 1994

Neonatal hepatitis with alpha-1-antitrypsin deficit. Apropos of a personal case. Annales d'Anatomie Pathologique 20(2): 159-176, 1975