Development, Vol 109, Issue 3 683-690, Copyright © 1990 by Company of Biologists

JOURNAL ARTICLES

Effects of the lethal yellow (Ay) mutation in mouse aggregation chimeras

GS Barsh, M Lovett and CJ Epstein
Department of Pediatrics, University of California, San Francisco 94143.

The Ay allele is a recessive lethal mutation at the mouse agouti locus, which results in embryonic death around the time of implantation. In the heterozygous state, Ay produces several dominant pleiotropic effects, including an increase in weight gain and body length, a susceptibility to hepatic, pulmonary and mammary tumors, and a suppression of the agouti phenotype, which results in a yellow coat color. To investigate the cellular action of Ay with regard to its effects upon embryonic viability and adult-onset obesity, we generated a series of aggregation chimeras using embryos that differ in their agouti locus genotype. Embryos derived from Ay/a x Ay/a matings were aggregated with those derived from A/A x A/A matings, and genotypic identification of the resultant chimeras was accomplished using a molecular probe at the Emv-15 locus that distinguishes among the three different alleles, Ay, A, and a. Among 50 chimeras, 25 analyzed as liveborns and 25 as 9.5 day embryos, 29 were a/a in equilibrium A/A and 21 were Ay/a in equilibrium A/A. The absence of Ay/Ay in equilibrium A/A chimeras demonstrates that Ay/Ay cells cannot be rescued in a chimeric environment, and the relative deficiency of Ay/a in equilibrium A/A chimeras suggests that, under certain conditions, Ay heterozygosity may partially affect cell viability or proliferation. In the 25 liveborn chimeras, Ay/a in equilibrium A/A animals became obese as adults and a/a in equilibrium A/A animals did not. There was no correlation between genotypic proportions and rate of weight gain, which shows that, with regard to its effects on weight gain, Ay heterozygosity is cell non-autonomous.

This article has been cited by other articles:

				D. Duhl, M. Stevens, H Vrieling, P. Saxon, M. Miller, C. Epstein, and G. Barsh Pleiotropic effects of the mouse lethal yellow (Ay) mutation explained by deletion of a maternally expressed gene and the simultaneous production of agouti fusion RNAs Development, January 6, 1994; 120(6): 1695 - 1708. [Abstract] [PDF]

				E J Michaud, S J Bultman, L J Stubbs, and R P Woychik The embryonic lethality of homozygous lethal yellow mice (Ay/Ay) is associated with the disruption of a novel RNA-binding protein. Genes & Dev., July 1, 1993; 7(7a): 1203 - 1213. [Abstract] [PDF]

				M W Miller, D M Duhl, H Vrieling, S P Cordes, M M Ollmann, B M Winkes, and G S Barsh Cloning of the mouse agouti gene predicts a secreted protein ubiquitously expressed in mice carrying the lethal yellow mutation. Genes & Dev., March 1, 1993; 7(3): 454 - 467. [Abstract] [PDF]