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Development, Vol 117, Issue 1 13-28, Copyright © 1993 by Company of Biologists

JOURNAL ARTICLES

Mice homozygous for a targeted disruption of the proto-oncogene int-2 have developmental defects in the tail and inner ear

SL Mansour, JM Goddard and MR Capecchi
Howard Hughes Medical Institute, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City 84112.

We derived mice that carry a targeted insertion of a neor gene in the int-2 (Fgf-3) proto-oncogene coding sequences. The mutation was found to be recessive and mice that were homozygous for the insertion did not often survive to adulthood. The mutant mice had defects in the development of the tail and inner ear that could be correlated with disruption of int-2 expression in the posterior primitive streak and hindbrain or otic vesicle. While the tail phenotype was 100% penetrant, we found that the inner ear phenotype had reduced penetrance and variable expressivity. The variable expressivity could not be attributed to variability in the genetic background of the mutant allele or to leaky expression from the mutant allele. Thus, we conclude that even in a uniform genetic background, stochastic variation in the expression of a developmental circuit can result in dramatic differences in phenotypic consequences.
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J. Rossant, B. Ciruna, and J. Partanen
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P. Xu, I Woo, H Her, D. Beier, and R. Maas
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S.-H. Oh, R. Johnson, and D. K. Wu
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R. A. Friedman
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T. Whitfield, M Granato, F. van Eeden, U Schach, M Brand, M Furutani-Seiki, P Haffter, M Hammerschmidt, C. Heisenberg, Y. Jiang, et al.
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J Malicki, A. Schier, L Solnica-Krezel, D. Stemple, S. Neuhauss, D. Stainier, S Abdelilah, Z Rangini, F Zwartkruis, and W Driever
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J. Barrow and M. Capecchi
Targeted disruption of the Hoxb-2 locus in mice interferes with expression of Hoxb-1 and Hoxb-4
Development, January 12, 1996; 122(12): 3817 - 3828.
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J. Goddard, M Rossel, N. Manley, and M. Capecchi
Mice with targeted disruption of Hoxb-1 fail to form the motor nucleus of the VIIth nerve
Development, January 10, 1996; 122(10): 3217 - 3228.
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S Nakai, H Kawano, T Yudate, M Nishi, J Kuno, A Nagata, K Jishage, H Hamada, H Fujii, and K Kawamura
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T Takeuchi, Y Yamazaki, Y Katoh-Fukui, R Tsuchiya, S Kondo, J Motoyama, and T Higashinakagawa
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M. Mathieu, P. Kiefer, I. Mason, and C. Dickson
Fibroblast Growth Factor (FGF) 3 from Xenopus laevis (XFGF3) Binds with High Affinity to FGF Receptor 2
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B Feldman, W Poueymirou, V. Papaioannou, T. DeChiara, and M Goldfarb
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M. Robinson, L. MacMillan-Crow, J. Thompson, and P. Overbeek
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R. Chow, G. Roux, M Roghani, M. Palmer, D. Rifkin, D. Moscatelli, and R. Lang
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Development, January 12, 1995; 121(12): 4383 - 4393.
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T. Lamb and R. Harland
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N. Manley and M. Capecchi
The role of Hoxa-3 in mouse thymus and thyroid development
Development, January 7, 1995; 121(7): 1989 - 2003.
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R Mahmood, P Kiefer, S Guthrie, C Dickson, and I Mason
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Development, January 5, 1995; 121(5): 1399 - 1410.
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P. Crossley and G. Martin
The mouse Fgf8 gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo
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D E Rancourt, T Tsuzuki, and M R Capecchi
Genetic interaction between hoxb-5 and hoxb-6 is revealed by nonallelic noncomplementation.
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T P Yamaguchi, K Harpal, M Henkemeyer, and J Rossant
fgfr-1 is required for embryonic growth and mesodermal patterning during mouse gastrulation.
Genes & Dev., December 15, 1994; 8(24): 3032 - 3044.
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C X Deng, A Wynshaw-Boris, M M Shen, C Daugherty, D M Ornitz, and P Leder
Murine FGFR-1 is required for early postimplantation growth and axial organization.
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