Journal Article

A New Spontaneous Mouse Mutation of <i>Hoxd13</i> with a Polyalanine Expansion and Phenotype Similar to Human Synpolydactyly

Kenneth R. Johnson, Hope O. Sweet, Leah Rae Donahue, Pat Ward-Bailey, Roderick T. Bronson and Muriel T. Davisson

in Human Molecular Genetics

Volume 7, issue 6, pages 1033-1038
Published in print June 1998 | ISSN: 0964-6906
Published online June 1998 | e-ISSN: 1460-2083 | DOI:
A New Spontaneous Mouse Mutation of Hoxd13 with a Polyalanine Expansion and Phenotype Similar to Human Synpolydactyly

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Human synpolydactyly (SPD) is an inherited congenital limb malformation caused by mutations in the HOXD13 gene. Heterozygotes are typically characterized by 3/4 finger and 4/5 toe syndactyly with associated duplicated digits; hands and feet of homozygotes are very small because of a shortening of the phalanges, metacarpal and metatarsal bones. Here we describe the phenotype and molecular basis of a spontaneous mutation of Hoxd13 in mice that provides a pheno-typically and molecularly accurate model for human SPD. The new mutation, named synpolydactyly homolog (spdh), is a 21 bp in-frame duplication within a polyalanine-encoding region at the 5′-end of the Hoxd13 coding sequence. The duplication expands the stretch of alanines from 15 to 22; the same type of expansion occurs in human SPD mutations. spdh/spdh homozygotes exhibit severe malformations of all four feet, including polydactyly, syndactyly and brachy-dactylia. The phenotype of spdh is much more severe than that exhibited by mice with a genetically engineered, presumably null, disruption of Hoxd13. Thus spdh probably acts in a dominant-negative manner and will be valuable for examining interactions with other Hox genes and their protein products during limb development. Homozygous mice of both sexes also lack preputial glands and males do not breed; therefore, spdh/spdh mice may also be valuable in studies of reproductive physiology and behavior.

Journal Article.  4139 words.  Illustrated.

Subjects: Genetics and Genomics

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