High Postnatal Lethality and Testis Degeneration in Retinoic Acid Receptor α Mutant Mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 15; pp. 7225 - 7229
• Main Authors: Lufkin, Thomas, Lohnes, David, Mark, Manuel, Dierich, Andree, Gorry, Philippe, Gaub, Marie-Pierre, LeMeur, Marianne, Chambon, Pierre
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.08.1993; National Acad Sciences; National Academy of Sciences
• Subjects: Alleles; Animals; Biological and medical sciences; Carrier Proteins - genetics; Carrier Proteins - physiology; Development Biology; Development. Metamorphosis. Moult. Ageing; Embryos; Exons; Fundamental and applied biological sciences. Psychology; Gene Expression; Genes, Lethal; Homozygotes; Lesions; Life Sciences; Male; Mice; Mutagenesis, Insertional; Protein isoforms; Receptors; Receptors, Retinoic Acid; Restriction Mapping; RNA; RNA, Messenger - genetics; Sertoli cells; Testes; Testis - growth & development; Tretinoin - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Nuclear receptor; Spermatogenesis; Mortality; Rodentia; Vitamin; Retinoids; Testicle; Male genital system; Postnatal development; Vertebrata; Phenotype; Mammalia; Gene; Mouse; Deletion; Degeneration; Retinoic acid; Biological receptor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.15.7225

Retinoic acid (RA) plays a critical role in normal development, growth, and maintenance of certain tissues. The action of RA is thought to be mediated in part by the three nuclear receptors (RARα, -β, and -γ), each of which is expressed as multiple isoforms. To investigate the function of the RARα gene, we have disrupted, in the mouse, the whole gene or the isoform RARα 1. Although RARα 1 is the predominant isoform and is highly conserved among vertebrates, RARα 1-null mice appeared normal. However, targeted disruption of the whole RARα gene resulted in early postnatal lethality and testis degeneration. These results, showing that RARα is indeed involved in the transduction of the RA signal, also suggest an unexpected genetic redundancy.