International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

B10. Characterization of an Insertional Mutation Responsible for Abnormal Limb Development

Dominique Simon-Chazottes,1 Sylvie Tutois,2 Franck Bourgade,1 Martin J. Evans,3 Michael R. Kuehn,4 and Jean-Louis Guénet1
1Unité de Génétique des Mammifères, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France,
Laboratoire de Génétique, Université de Clermont-Ferrand, France,
Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, United Kingdom,
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA

An autosomal recessive mutation characterized by abnormal digitation (dan) was discovered in the progeny of a female mouse derived from a transgenic founder obtained by experimental infection of ES cells with a defective MPSV neo retroviral vector. Homozygous mice show fusion of the medium digits and are smaller than their unaffected littermates. We mapped dan mutation to mouse chromosome 2, in the vicinity of homeobox gene Hoxd, but found recombinants with this locus. The level of expression of this new gene was studied by Northern blot analysis in various tissues, and also in the developping limb bud between 10.5 and 12.5 d.p.c. We cloned the flanking region of the retroviral insertion and found that the retrovirus was inserted in the first intron of a gene coding for a lipoprotein receptor. Expression of the gene is turned off by the insertion of proviral genome. Mutation in this new gene have certainly effect on cell cholesterol uptake and may interact with the sonic hedgehog pathway.

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