RNA-Seq expression data from the reproductive tracts of WT, Hoxa91011, and Hoxd91011 mutant mice

Hox genes are key regulators of development. In mammals, the study of these genes is greatly confounded by their large number, overlapping functions, and their interspersed shared enhancers. In this report, we describe a novel recombineering strategy that was used to introduce simultaneous frameshift mutations into the flanking Hoxa9, Hoxa10, and Hoxa11 genes, as well as their paralogs on the HoxD cluster. The resulting mutant mice displayed dramatic homeotic transformations of the reproductive tracts, with uterus anteriorized towards oviduct and the vas deferens anteriorized towards epididymis. The Hoxa9,10,11 mutant mice provided a sensitized genetic background that allowed the discovery of Hoxd9,10,11 reproductive tract patterning function. Both shared and distinct Hox functions were defined. The HoxD genes played a crucial role in the regulation of the uterine immune function. Non-coding nonpolyadenylated RNAs were among the key Hox targets. In addition we observed a surprising anti-dogmatic posteriorization of the uterine epithelium. Overall design: Reproductive tracts were collected from WT and Hox mutant mice (n=3/genotype) aged 3-7 months in order to characterize the molecular changes caused by mutation of Hoxa9,10,11 and Hoxd9,10,11. Female mice were staged and collected in diestrus.

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Raines AM, Adam M, Magella B, Meyer SE, Grimes HL, Dey SK, Potter SS