• NOTUM is a phospholipase that is thought to involve in negative regulation of Wnt signaling pathway through the removal of an essential palmitoleate group from Wnt proteins. NOTUM plays an important role in human disease, such as cancer、osteoporosis and neurodegenerative disorders.
• Mature human NOTUM is 496 amino acids (aa) in length, which shares 89% aa sequence identity with mouse NOTUM.
• The exons 2-12 of mouse Notum gene that encode the whole molecule, including 3’UTR were replaced by human counterparts in B-hNOTUM mice. The promoter and 5’UTR region of the mouse gene are retained. The human NOTUM expression is driven by endogenous mouse Notum promoter, while mouse Notum gene transcription and translation will be disrupted.
• Mouse Notum mRNA was only detectable in wild-type C57BL/6N mice. Human NOTUM mRNA was exclusively detectable in homozygous B-hNOTUM mice.
• Human NOTUM was exclusively detectable in serum of homozygous B-hNOTUM mice but not wild-type mice.
• This product is used for pharmacodynamics and safety evaluation of drugs.

Gene targeting strategy for B-hNOTUM mice. The exons 2-12 of mouse Notum gene that encode the whole molecule are replaced by human counterparts in B-hNOTUM mice. The promoter and 5’UTR region of the mouse gene are retained, but the 3’UTR region of the mouse gene are replaced by human counterparts. The NOTUM expression is driven by endogenous mouse Notum promoter, while mouse Notum gene transcription and translation will be disrupted.

Species specific analysis of NOTUM gene expression in wild-type C57BL/6N mice and homozygous humanized B-hNOTUM mice by RT-PCR. Liver were collected from wild-type C57BL/6N mice (+/+) and homozygous B-hNOTUM mice (H/H). Mouse Notum mRNA was detectable only in wild-type C57BL/6N mice. Human NOTUM mRNA was detectable only in homozygous B-hNOTUM mice, but not in wild-type C57BL/6N mice.

Strain specific NOTUM expression analysis in wild-type C57BL/6N mice and homozygous humanized B-hNOTUM mice by ELISA. Serum was collected from wild-type C57BL/6N mice (+/+) and homozygous B-hNOTUM mice (H/H). Expression level of human NOTUM were analyzed by ELISA (anti-human NOTUM ELISA Kit: Abcam, ab317781). Human NOTUM was exclusively detectable in homozygous B-hNOTUM mice but not wild-type C57BL/6N mice. Values are expressed as mean ± SEM. ND: not detectable.