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. 2018 Apr 20;8:6306. doi: 10.1038/s41598-018-24782-5

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Hox mutant kidneys exhibit hypoplasia, dysplasia, and bilateral agenesis as well as severely cystic kidneys. (a) Gross dissections showed smaller kidneys in Hoxc9,10,11−/− and all heterozygous/homozygous combinations generated (Hoxa9,10,11+/− Hoxc9,10,11−/−, Hoxa9,10,11−/− Hoxc9,10,11+/−, Hoxc9,10,11−/− Hoxd9,10,11+/−, Hoxc9,10,11+/− Hoxd9,10,11−/− as well as triple heterozygotes Hoxa9,10,11+/− Hoxc9,10,11+/− Hoxd9,10,11+/−). Hoxc9,10,11−/− Hoxd9,10,11−/− and Hoxa9,10−/−11+/− Hoxc9,10,11−/− mutants showed very small, rudimentary kidneys and Hoxa9,10,11−/− Hoxc9,10,11−/− showed bilateral renal agenesis. N = 8 for each genotype; arrow – gonads, arrowhead – bladder, asterisk – adrenal gland. (b) Representative H&E images of E18.5 all heterozygous/homozygous mutants generated (genotypes listed above) showed hypoplasia (P’,T’). We observed occasional cystic tubules and dilated Bowmen’s space (T’; asterisk). Hoxc9,10,11−/− Hoxd9,10,11−/− and Hoxa9,10−/−11+/− Hoxc9,10,11−/− mutant kidneys appeared dysplastic, with lobar disorganization (M’,N’) and tubules surrounded by stroma (U’, arrows). E18.5 Hoxa9,10−/−11+/− Hoxc9,10,11−/− mutants lacked a nephrogenic zone (R’; arrowhead), whereas residual areas of nephrogenesis were present in Hoxc9,10,11−/− Hoxd9,10,11−/− mutants (Q’). Hoxa9,10−/−11+/− Hoxc9,10,11−/− mutants also demonstrated dysplastic epithelium in the renal papilla (V’; asterisk). Magnification bar = 50 μm; N = 3 for each genotype. (c) Gross images (W’-Y’; original magnification 6x) and H&Es (Z’-BB’ original magnification 2x; CC’-EE’ original magnification 20x) showed that 10–15% of 2 month old heterozygous/homozygous multi-Hox mutant mice (N = 40 mice total) and all surviving Hoxc9,10,11−/− Hoxd9,10,11−/− mutants (N = 3) developed cystic kidneys.