Anti-WNT9B monoclonal antibody Made to order

Wnt signaling is essential for the maintenance of adult stem cells and its aberrant activation is a stimulator of carcinogenesis. The transmembrane protein, Wntless, is an essential Wnt signaling component through regulating the secretion of Wnt ligands. Here, we generated a mouse model with specific Wntless knockout in intestinal epithelium to study its function in the intestinal epithelium. Wntless knockout exhibits no obvious defects in mice but significantly disrupted proliferation and differentiation of small intestinal organoids. We also discovered that these deficiencies could be partially rescued by Wnt3a supplement but not Wnt9b. To further investigate the role of Wntless in tumorigenesis, APC-deficient spontaneous intestinal tumors and chemical induced colorectal cancer mouse models were employed. To our surprise, intestinal epithelium-specific knockout of Wntless did not cause significant differences in tumor number and size. In summary, our data demonstrated that epithelial Wntless was required for the growth and differentiation of small intestinal organoids but not in live animals, suggesting the other tissues, such as mesenchymal tissue, play critical role for Wnt secretion in both intestinal homeostasis as well as tumorigenesis. (C) 2019 Elsevier Inc. All rights reserved.

Background: Wntl 1 is a member of the Wnt family of secreted signals controlling the early steps in ureteric bud (UB) branching. Due to the reported lethality of VVnt11 knockout embryos in utero, its role in later mammalian kidney organogenesis remains open. The presence of Wntl 1 in the emerging tubular system suggests that it may have certain roles later in the development of the epithelial ductal system. Results: The Wnt11 knockout allele was backcrossed with the 057816 strain for several generations to address possible differences in penetrance of the kidney phenotypes. Strikingly, around one third of the null mice with this inbred background survived to the postnatal stages. Many of them also reached adulthood, but urine and plasma analyses pointed out to compromised kidney function. Consistent with these data the tubules of the C57816 Wnt11 mice appeared to be enlarged, and the optical projection tomography indicated changes in tubular convolution. Moreover, the C57816 Wnt11(-/-) mice developed secondary glomerular cysts not observed in the controls. The failure of Wnt11 signaling reduced the expression of several genes implicated in kidney development, such as Wnt9b, Six2, Foxd1 and Hoxid. Also Dvl2, an important PCP pathway component, was downregulated by more than 90 % due to Wnt11 deficiency in both the E16.5 and NB kidneys. Since all these genes take part in the control of UB, nephron and stromal progenitor cell differentiation, their disrupted expression may contribute to the observed anomalies in the kidney tubular system caused by Wnt11 deficiency. Conclusions: The Wntl 1 signal has roles at the later stages of kidney development, namely in coordinating the development of the tubular system. The C571316 Wnt11(-/-) mouse generated here provides a model for studying the mechanisms behind tubular anomalies and glomerular cyst formation.