B-hPNPLA3*I148M mice
| Strain Name |
C57BL/6-Pnpla3tm1(PNPLA3*I148M)Bcgen/Bcgen
|
Common Name | B-hPNPLA3*I148M mice |
| Background | C57BL/6 | Catalog number |
112965 |
|
Related Genes |
ADPN, C22orf20, iPLA(2)epsilon |
||
|
NCBI Gene ID |
80339 | ||
模型验证
Description
Targeting strategy
mRNA expression analysis
Protein expression analysis
Inhibitory efficiency of the nucleic acid drugs against the human PNPLA3
- PNPLA3 (patatin-like phospholipase domain-containing protein 3) is a lipid-metabolizing enzyme with roles primarily linked to lipid homeostasis and disease pathogenesis.
- The exons 1-9 of mouse Pnpla3 gene that encode the whole molecule (ATG to STOP codon), including 5’UTR, 3’UTR and promoter, were replaced by their human counterparts with the I148M mutation in B-hPNPLA3*I148M mice.
- Mouse Pnpla3 mRNA was only detectable in wild-type C57BL/6 mice, and human PNPLA3 mRNA was exclusively detectable in homozygous B-hPNPLA3*I148M mice but not in wild-type C57BL/6 mice.
- PNPLA3 was detectable in heart, liver, spleen, kidney, skin and adipose of wild-type C57BL/6 mice and homozygous B-hPNPLA3*I148M mice due to the cross-reactivity of antibody.
- B-hPNPLA3*I148M mice provide a powerful preclinical model for in vivo evaluation of human PNPLA3 targeted nucleic acid drugs.
Gene targeting strategy for B-hPNPLA3*I148M mice. The exons 1-9 of mouse Pnpla3 gene that encode the whole molecule (ATG to STOP codon), including 5’UTR, 3’UTR and promoter, were replaced by their human counterparts with the I148M mutation in B-hPNPLA3*I148M mice.
Strain specific analysis of PNPLA3 mRNA expression in wild-type C57BL/6 mice and B-hPNPLA3*I148M mice by RT-PCR. Liver RNA was isolated from wild-type C57BL/6 mice (+/+) and homozygous B-hPNPLA3*I148M mice (H/H). Mouse Pnpla3 mRNA was only detectable in wild-type C57BL/6 mice, and human PNPLA3 mRNA was exclusively detectable in homozygous B-hPNPLA3*I148M mice but not in wild-type C57BL/6 mice.
Strain specific PNPLA3 expression analysis in wild-type C57BL/6 mice and humanized B-hPNPLA3*I148M mice by Western blot. Various tissue lysates were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hPNPLA3*I148M mice (H/H), and then analyzed by western blot with anti-PNPLA3 antibody (Proteintech, 67369-1-Ig). PNPLA3 was detectable in heart, liver, spleen, kidney, skin and adipose of wild-type C57BL/6 mice and homozygous B-hPNPLA3*I148M mice due to the cross-reactivity of antibody.
The inhibitory efficiency of the nucleic acid drugs against human PNPLA3 in heterozygous B-hPNPLA3*I148M mice. The human PNPLA3 targeted nucleic acid drugs (provide by client) and PBS were administered to the B-hPNPLA3*I148M mice individually on day 1. The mice were sacrificed on day 8, and the liver tissue was collected to detect the expression level of human PNPLA3 mRNA by qPCR. The human PNPLA3 mRNA in the treatment groups (siRNA) were significantly reduced compared to the control groups (PBS), demonstrating that B-hPNPLA3*I148M mice provide a powerful preclinical model for in vivo evaluation of human PNPLA3 targeted nucleic acid drugs. Values are expressed as mean ± SEM.
Note: This experiment was performed by the client using B-hPNPLA3*I148M mice. All the other materials were provided by the client.
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