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Editor—Homeobox (Hox) gene products are characterised by the presence of a highly conserved 20 amino acid region (homeodomain) known to bind specific DNA sequences. They promote the expression of downstream genes, thus controlling morphogenesis and cell differentiation in the developing embryo.1 Hox11l1 is also namedNcx,2 3 Enx,4 pmur10f,5 and reported asTlx-2 in the Mouse Genome Database (MGD,http://www.informatics.jax.org). Hox11l1 is a member of the Hox11 unclustered homeobox genes, a family characterised by a novel homeodomain with threonine replacing isoleucine or valine at a critical site (residue 48 in the third helix); this alters the DNA recognition motif, which may identify a unique set of target genes.5 Hox11l1 expression is detectable in mice in the E9.5 to the E12.5 stages of development and involves dorsal root ganglia, cranial (V, IX, X) and enteric nerve ganglia, adrenal glands in embryos, and adrenal glands and intestine in adult mice. Since its expression is limited to tissues derived from neural crest cells,Hox11l1 may play a role in the proliferation or differentiation of neural crest cell lines.2
Two different Hox11l1 knock out mouse models have been generated.3 4 In both cases homozygous mutant mice were viable but developed megacolon at the age of 3-5 weeks. Histological and immunohistochemical analysis showed hyperplasia of myenteric ganglia, a phenotype similar to that observed in a human congenital intestinal disorder named intestinal neuronal dysplasia (IND).6 7
There are two clinically and histologically distinguishable subtypes of IND. Type A (IND type A, MIM 243180), occurring in less than 5% of cases, is characterised by congenital aplasia or hypoplasia of the sympathetic innervation and presents acutely in the neonatal period with episodes of intestinal obstruction, diarrhoea, and bloody stools. Type B (IND type B, MIM …