Mouse Mutants Carrying Deletions that Remove the Genes Mutated in Coffin-Lowry Syndrome and Lactic Acidosis

Abstract

The mouse X-linked mutants lined and stripey are associated with lethality of affected males in utero and a striping of the coat in carrier females. We demonstrate that the underlying mutations are nested deletions which lie in the Phex-Amelx chromosomal segment conserved between man and mouse. The lined deletion contains less than ∼0.7 cM of genetic material and includes the growth factor-regulated protein kinase gene, Rsk2. Stripey carries a larger deletion which removes ∼2.0 cM of genetic material, including Rsk2 and the pyruvate dehydrogenase E1 a subunit gene, Pdha1. Since Coffin-Lowry syndrome and neonatal lactic acidosis are associated with mutations in the human homologues of Rsk2 and Pdha1 respectively, lined and stripey provide models for gene deficiencies in these disorders.