The homeodomain transcription factor Nkx2-3 is expressed in gut mesenchyme and spleen of embryonic and adult mice. Targeted inactivation of the Nkx2-3 gene results in severe morphological alterations of both organs and early postnatal lethality in the majority of homozygous mutants. Villus formation in the small intestine appears considerably delayed in Nkx2-3(−)/- foetuses due to reduced proliferation of the epithelium, while massively increased growth of crypt cells ensues in surviving adult mutants. Interestingly, differentiated cell types of the intestinal epithelium are present in homozygous mutants, suggesting that Nkx2-3 is not required for their cell lineage allocation or migration-dependent differentiation. Hyperproliferation of the gut epithelium in adult mutants is associated with markedly reduced expression of BMP-2 and BMP-4, suggesting that these signalling molecules may be involved in mediating non-cell-autonomous control of intestinal cell growth. Spleens of Nkx2-3 mutants are generally smaller and contain drastically reduced numbers of lymphatic cells. The white pulp appears anatomically disorganized, possibly owing to a homing defect in the spleen parenchyme. Moreover, some of the Nkx2-3 mutants exhibit asplenia. Taken together these observations indicate that Nkx2-3 is essential for normal development and functions of the small intestine and spleen.

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