NDRG4 is a member of the NDRG family (N-myc downstream-regulated gene), which is highly expressed in brain and heart. Previous studies showed that Ndrg1-deficient mice exhibited a progressive demyelinating disorder of peripheral nerves and Ndrg4-deficient mice had spatial learning deficits and vulnerabilities to cerebral ischemia. Here, we report generation of Ndrg4 mutant alleles that exhibit several development defects different from those previously reported. Our homozygous mice showed growth retardation and postnatal lethality. Spleen and thymuses of Ndrg4(-/-) mice are considerably reduced in size from 3 weeks of age. Histological analysis revealed abnormal hyperkeratosis in the squamous foregut and abnormal loss of erythrocytes in the spleen of Ndrg4(-/-) mice. In addition, we observed an abnormal hind limb clasping phenotype upon tail suspension suggesting neurological abnormalities. Consistent to these abnormalities, Ndrg4 is expressed in smooth muscle cells of the stomach, macrophages of the spleen and neurons. Availability of the conditional allele for Ndrg4 should facilitate further detailed analyses of the potential roles of Ndrg4 in gut development, nervous system and immune system. (C) 2016 Elsevier Inc. All rights reserved.