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Molecular and Cellular Biology, December 1998, p. 7455-7465, Vol. 18, No. 12
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Strain-Dependent Myeloid Hyperplasia, Growth Deficiency, and Accelerated Cell Cycle in Mice Lacking the Rb-Related p107 Gene

Jennifer E. LeCouter, Boris Kablar, W. Rodney Hardy, Chuyan Ying, Lynn A. Megeney, Linda L. May, and Michael A. Rudnicki*

Institute for Molecular Biology and Biotechnology, McMaster University, Hamilton, Ontario, Canada L8S 4K1

Received 19 May 1998/Returned for modification 30 June 1998/Accepted 28 August 1998

To investigate the function of the Rb-related p107 gene, a null mutation in p107 was introduced into the germ line of mice and bred into a BALB/cJ genetic background. Mice lacking p107 were viable and fertile but displayed impaired growth, reaching about 50% of normal weight by 21 days of age. Mutant mice exhibited a diathetic myeloproliferative disorder characterized by ectopic myeloid hyperplasia in the spleen and liver. Embryonic p107-/- fibroblasts and primary myoblasts isolated from adult p107-/- mice displayed a striking twofold acceleration in doubling time. However, cell sort analysis indicated that the fraction of cells in G1, S, and G2 was unaltered, suggesting that the different phases of the cell cycle in p107-/- cells was uniformly reduced by a factor of 2. Western analysis of cyclin expression in synchronized p107-/- fibroblasts revealed that expression of cyclins E and A preceded that of D1. Mutant embryos expressed approximately twice the normal level of Rb, whereas p130 levels were unaltered. Lastly, mutant mice reverted to a wild-type phenotype following a single backcross with C57BL/6J mice, suggesting the existence of modifier genes that have potentially epistatic relationships with p107. Therefore, we conclude that p107 is an important player in negatively regulating the rate of progression of the cell cycle, but in a strain-dependent manner.

* Corresponding author. Mailing address: Institute for Molecular Biology and Biotechnology, McMaster University, Hamilton, Ontario, Canada L8S 4K1. Phone: (905) 525-9140, ext. 27424. Fax: (905) 521-2955. E-mail: rudnicki{at}mcmaster.ca.

Molecular and Cellular Biology, December 1998, p. 7455-7465, Vol. 18, No. 12
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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