Disruption of Gen1 causes ectopic budding and kidney hypoplasia in mice.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a family of often-concurrent diseases with various anatomical spectra. Null-mutant Gen1 mice frequently develop multiple urinary phenotypes, most commonly duplex kidneys, and are ideal subjects for research on ectopic budding in CAKUT development. The upper and lower kidney poles of the Gen1 PB/PB mouse were examined by histology, immunofluorescence, and immunohistochemistry. The newborn Gen1 PB/PB mouse lower poles were significantly more hypoplastic than the corresponding upper poles, with significantly fewer glomeruli. On embryonic day 14.5, immediately before first urine formation, the upper pole kidney was already larger than the lower pole kidney. In vivo and in vitro, embryonic kidney upper poles had more ureteric buds than lower poles. Gen1 PB/PB embryos exhibited ectopic ureteric buds, usually near the original budding site, occasionally far away, or, rarely, derived from the primary budding site. Therefore, ectopia of the ureteric buds is the core of CAKUT formation. Further studies will be needed to investigate the regulatory roles of these genes in initial ureteric budding and subsequent ontogenesis during metanephros development. • Ectopia of the initial budding is central to the formation of CAKUT. • Three kinds of ectopic bud develop into three duplex kidneys in Gen1 PB/PB mice. • Upper pole kidney of newborn Gen1 PB/PB mice was more hypoplastic than that in lower. • At E14.5, the upper pole kidney was already larger than the lower pole kidney. • Ectopic budding alone results in kidney hypoplasia, not dysplasia in Gen1 mutation. [ABSTRACT FROM AUTHOR]