The murine t complex on chromosome 17 contains a number of homozygous lethal and semi-lethal
mutations that disrupt development of the mouse embryo. We recently characterized an embryonic
lethality in the rat that results from a germ-line mutation in the tuberous sclerosis 2 (Tsc-2)
tumour suppressor gene (the Eker mutation). Remarkably, mouse embryos homozygous for tw8
mutation display cranial defects reminiscent of those observed in rat embryos homozygous for the
Eker mutation. To determine whether the Tsc-2 gene, which is in the t
complex, is mutated in tw8
or other t haplotypes, we characterized this gene in a series of
t haplotype mice. Four Tsc-2
polymorphisms were identified: three in the coding region and one intronic that appeared to be
common to all t haplotypes analysed. No evidence was found to argue that the Tsc-2 gene is
altered in tw8 haplotype mice. However, in the
tw5 haplotype we found a G to T mutation in Tsc-2
that was present only in this t haplotype. In contrast to other polymorphisms within the Tsc-2
coding region which did not result in amino acid changes in Tsc-2 gene product tuberin, this
mutation substituted a phenylalanine for a conserved cysteine in tw5
tuberin. Within the t complex, the Tsc-2 gene and the putative
tw5 locus appeared to map to different positions, complicating
identification of Tsc-2 as a candidate for the tw5
locus and suggesting that the G to T mutation in
the Tsc-2 gene may have arisen independently of the tw5
functional mutation.