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Research objectives

Genetics of mammalian development

We investigate fundamental processes that direct mammalian embryonic development. To this end we take advantage of the mouse as an in vivo model system, utilising two different genetic approaches.

Forward genetics
We have initiated a forward screen for developmental mutations. This involves backcrossing of mutagen-treated mice, followed by identification of mutant lines on the basis of observed malformed embryos. This approach has allowed identification of a number of new mutants that we are currently analysing and mapping (collaboration with the Cuppen group in the Institute). In these mutants we see neural tube closure defects (fig. 1), cardiac malformations (fig. 2) and early gastrulation defects.

Reverse genetics

Using gene targeting technology we have inactivated members of the ‘aristaless' family of paired-type homeobox genes, and characterised the resulting skeletal (fig. 5 and 6) and cardiac defects.

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Figure 1: Exencephaly in mutant line 5120-6.

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Figure 2: abnormal folding of heart tube, thoracic edema,
fused branchial arches in mutant line 5120-7

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Figure 3

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Figure 4

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Figure 5: skulls (lower jaw removed)  of   wildtype (l) and Alx3/Alx4 double mutant (r).

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Figure 6: polydactyly in Alx mutant.