Although the gross appearance of mutant kidneys was not significantly different from that of control kidneys at P0 (Figure 2B), the mutant mice exhibited nephrotic-level proteinuria on P0 (Figure 2C) and throughout their lives (data not shown).
The apparent failure of the ureteric bud to reach the mesenchyme in Lrp4 mutant kidneys is similar to what has been observed in mice with defects in GDNF/Ret signaling [24].
Having now found that Fras1 was expressed by foetal podocytes, mutant kidneys were re-examined with a focus on glomeruli.
Wild-type and mutant kidneys were lysed, total RNA was extracted (RNEasy Micro kit; Qiagen, Germantown, MD), processed and hybridized to the GeneChip Mouse Genome 430 2.0 microarray (Affymetrix) by the UCSD genechip core by as previously described (Choi et al., 2009; Tee et al., 2010).
Signal obtained from control kidney samples were used as an experiment to compare to the signal obtained from Lim1 conditional mutant kidneys that was designated as a baseline.
We show that betaglycan mutant kidney phenotypes are similar to the previously characterized Tgfb2 mutant phenotypes.
Possibly the kidneys are implicated.
This may be due to reduced TGFβ sensitivity in the betaglycan mutant kidneys as TGFβs are well-recognized to auto-induce their own expression by both transcriptional and post-transcriptional mechanisms [36], [37].
In addition to kidney cysts, duplex kidneys were also observed in Mks1-mutant animals.
