Publication Date:
1988-12-09
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dycaico, M J -- Grant, S G -- Felts, K -- Nichols, W S -- Geller, S A -- Hager, J H -- Pollard, A J -- Kohler, S W -- Short, H P -- Jirik, F R -- N01-HR-56024/HR/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1988 Dec 9;242(4884):1409-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, CA 90048.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3264419" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
Animals
;
Animals, Newborn
;
Disease Models, Animal
;
*Genes
;
Hepatitis/congenital/*genetics/pathology
;
Humans
;
Liver/pathology
;
Mice
;
Mice, Inbred Strains
;
Mice, Transgenic
;
*Mutation
;
alpha 1-Antitrypsin/*genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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