• APOB is the main apolipoprotein of chylomicrons and low density lipoproteins. It occurs in plasma as two main isoforms, apoB-48 and apoB-100, which encoded by a single gene APOB, the shorter apoB-48 protein is produced after RNA editing of the apoB-100 transcript at residue 2180 (CAA->UAA) and early translation termination. Apob-48 is is synthesizedin gut and apoB-100 in liver. 
• The exons 1-29 of mouse Apob gene that encode the whole molecule (ATG to STOP codon), including 5’UTR and 3’UTR were replaced by human counterparts in B-hAPOB mice. The human APOB expression is driven by human APOB promoter, while mouse Apob gene transcription and translation will be disrupted. 
• ApoB-48 is secreted by the intestine to become a component of chylomicrons, while ApoB-100 is secreted by the liver to become a component of very low-density lipoproteins (VLDLs), intermediate-density lipoproteins (IDLs), and low-density lipoproteins (LDLs).
• Human APOB was exclusively detectable in heterozygous B-hAPOB mice (H/+).
• More than 100 mutations in the APOB gene are known to cause familial hypercholesterolemia. This condition is characterized by very high levels of cholesterol in the blood and an increased risk of developing heart disease.
• B-hAPOB mice could mate with B-hLPA mice to form human Lp(a) complex.

Gene targeting strategy for B-hAPOB mice. The exons 1-29 of mouse Apob gene that encode the whole molecule (ATG to STOP codon), including 5’UTR and 3’UTR were replaced by human counterparts in B-hAPOB mice. The human APOB expression is driven by human APOB promoter, while mouse Apob gene transcription and translation will be disrupted. 

Strain specific analysis of APOB mRNA expression in wild-type mice and B-hAPOB mice by RT-PCR. Liver RNA were isolated from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hAPOB mice (H/H). Mouse Apob mRNA was only detectable in wild-type C57BL/6JNifdc mice, and human APOB mRNA was exclusively detectable in homozygous B-hAPOB mice but not in wild-type C57BL/6JNifdc mice. 

Strain-specific APOB expression analysis in wild-type C57BL/6JNifdc mice and homozygous humanized B-hAPOB mice by ELISA. Serum was collected from wild-type C57BL/6JNifdc mice (+/+) (female, n=3, 6 weeks old) and homozygous B-hAPOB mice (H/H) (female, n=3, 6 weeks old). Expression level of mouse and human APOB were analyzed by ELISA (Mouse APOB ELISA Kit: Abcam, ab230932; Human Apolipoprotein B ELISA Kit (APOB): Abcam, ab108807). Mouse APOB was only detectable in wild-type C57BL/6Nidfc mice but not in B-hAPOB mice. Human APOB was exclusively detectable in homozygous B-hAPOB mice but not in C57BL/6Nidfc mice. Values are expressed as mean ± SEM.