What happens when all six alleles of Hox11 paralogues are knocked out in mice?
Hox11 paralogues Hoxa11, Hoxc11 and Hoxd11 redundantly pattern the zeugopod intermediate segment. Individual or double knockouts display mild radius ulna or tibia fibula shortening, reflecting dosage compensation and functional overlap. Progressive allele loss reveals quantitative dependence, and eliminating all six alleles results in complete loss of zeugopod elements while stylopod humerus femur dependent on Hox9 and autopod dependent on Hox12-13 remains largely intact. This demonstrates regional specificity, redundancy, and dosage sensitivity, explaining why full Hox11 null phenotype is defined by dramatic zeugopod agenesis.
Ref: Wellik and Capecchi, Science 2003, Hox11 paralogous group specifies zeugopod region formation.