The minor spliceosome is required for limb growth but not patterning

Diseases caused by mutations in components of the minor spliceosome frequently result in primordial dwarfism, where the limbs are stunted in size but retain pattern. We therefore sought to determine the role of the minor splieceosome in limb development by ablating an essential component, Rnu11, which encodes the U11 snRNA, in the mouse limb bud through Prrx1-Cre. We found that loss of U11 results in severe reduction in limb size at birth. However, mutant limbs retain proximo-distal patterning. Thus, we performed total RNAseq at E10.5 and E11.5 for both WT and mutant forelimb and hindlimb to determine the underlying molecular consequence of U11 loss and its effect on gene expression in the developing limb. Overall design: Total mRNA profiles of forelimb (FL) and hindlimb (HL) buds dissected from E10.5 and E11.5 n=3 WT and mutant mice through TruSeq stranded total RNA prep followed by Illumina NextSeq500 with high output.