• FGFR3 is highly expressed in chondrocytes and osteoblasts, playing a negative regulatory role in bone development and skeletal maintenance. Achondroplasia (ACH) is caused by mutations in the FGFR3 gene, which lead to constitutive activation of FGFR3, thereby inhibiting the proliferation and differentiation of chondrocytes.
• Gene editing strategy: The exons 2-18 of mouse Fgfr3 gene that encode the whole molecule (ATG to STOP codon), including 3’UTR were replaced by human counterparts in B-hFGFR3*G380R mice. The promoter and 5’UTR region of the mouse gene are retained. The human FGFR3 expression is driven by endogenous mouse Fgfr3 promoter, while mouse Fgfr3 gene transcription and translation will be disrupted.
• mRNA expression analysis: Mouse Fgfr3 mRNA were both detectable in wild-type C57BL/6 mice and heterozygous B-hFGFR3*G380R mice. Human FGFR3 mRNA was detectable only in heterozygous B-hFGFR3*G380R mice but not in wild-type mice.
• Phenotypic analysis: Heterozygous B-hFGFR3*G380R mice (6-week-old) exhibit a short body, rounded head, short snout, curved spine and protruding incisors.
• Application: This product is used for pharmacodynamics evaluation of Achondroplasia (ACH).

Gene targeting strategy for B-hFGFR3*G380R mice. The exons 2-18 of mouse Fgfr3 gene that encode the whole molecule (ATG to STOP codon), including 3’UTR were replaced by human counterparts in B-hFGFR3*G380R mice. The promoter and 5’UTR region of the mouse gene are retained. The human FGFR3 expression is driven by endogenous mouse Fgfr3 promoter, while mouse Fgfr3 gene transcription and translation will be disrupted.

Strain specific analysis of FGFR3 mRNA expression in wild-type C57BL/6 mice and B-hFGFR3*G380R mice by RT-PCR. Skin RNA were isolated from wild-type C57BL/6 mice (+/+) and heterozygous B-hFGFR3*G380R mice (H/+), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human FGFR3 primers. Mouse Fgfr3 mRNA were both detectable in wild-type C57BL/6 mice and heterozygous B-hFGFR3*G380R mice. Human FGFR3 mRNA was detectable only in heterozygous B-hFGFR3*G380R mice but not in wild-type mice.

Phenotypic analysis of heterozygous B-hFGFR3*G380R mice: Heterozygous B-hFGFR3*G380R mice (6-week-old) exhibit a short body, rounded head, short snout, curved spine and protruding incisors.

Micro-CT  analysis of heterozygous B-hFGFR3*G380R mice: The length of the femurs and tibiae in heterozygous B-hFGFR3*G380R mice (6-week-old) are significantly shorter than those in the wild-type C57BL/6JNifdc mice (6-week-old).