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M J Justice

Publications and source records attributed to M J Justice.

57 records · Page 4Linked to original sources

Genetic analysis of mouse t haplotypes using mutations induced by ethylnitrosourea mutagenesis: the order of T and qk is inverted in t mutants.

The t region of mouse chromosome 17 exhibits recombination suppression with wild-type chromatin. However, the region has resisted classical genetic dissection because of a lack of defined variants. Mutations induced by N-ethyl-N-nitrosourea (ENU) at the Brachyury (T), quaking (qk), and tufted (tf) loci of the mouse tw5 haplotype have now allowed the analysis of crossovers between two complete t haplotypes. A classical breeding analysis of the complete t haplotypes, tw5 and t12, utilizing the newly induced markers, reveals two inversions in t chromatin: one involving T and qk, and one involving tf and the H-2 complex. Moreover, the recombination frequency between the loci of T and qk is reduced compared to the frequency reported in normal chromatin. These two inversions are a sufficient explanation for the recombination inhibition with normal chromatin exhibited by t haplotypes isolated from the wild. Furthermore, the reduced recombination frequency between T and qk may indicate that the proximal gene rearrangement is not a simple inversion.

Animals↗

Gene defect in ectodermal dysplasia implicates a death domain adapter in development.

Members of the tumour-necrosis factor receptor (TNFR) family that contain an intracellular death domain initiate signalling by recruiting cytoplasmic death domain adapter proteins. Edar is a death domain protein of the TNFR family that is required for the development of hair, teeth and other ectodermal derivatives. Mutations in Edar-or its ligand, Eda-cause hypohidrotic ectodermal dysplasia in humans and mice. This disorder is characterized by sparse hair, a lack of sweat glands and malformation of teeth. Here we report the identification of a death domain adapter encoded by the mouse crinkled locus. The crinkled mutant has an hypohidrotic ectodermal dysplasia phenotype identical to that of the edar (downless) and eda (Tabby) mutants. This adapter, which we have called Edaradd (for Edar-associated death domain), interacts with the death domain of Edar and links the receptor to downstream signalling pathways. We also identify a missense mutation in its human orthologue, EDARADD, that is present in a family affected with hypohidrotic ectodermal dysplasia. Our findings show that the death receptor/adapter signalling mechanism is conserved in developmental, as well as apoptotic, signalling.

Amino Acid Sequence↗