Nomenclature: C57BL/6NTac-Atp7b^{tm7876(ATP7B*H1069Q)Tac}

• The targeting strategy allows the generation of a constitutive humanization of the Atp7b gene.
• The targeting strategy is based on NCBI transcripts NM_007511.2 (mouse) and NM_000053.4 (human).
• Exon 1 contains the translation initiation codon.
• Mouse genomic sequence from the translation initiation codon in exon 1 to the translation termination codon in exon 21 has been replaced with its human counterpart. The mouse and human nucleotide sequence is identical for the last amino acid I1462 in exon 21. The mouse nucleotide sequence has been used for this codon.
• The point mutation H1069Q (rs76151636; according to the human annotation) has been inserted into human exon 14.
• Positive selection markers have been flanked by FRT (Neomycin resistance - NeoR) and F3 (Puromycin resistance - PuroR) sites and have been inserted into intron 1 and intron 13.
• The targeting vector has been generated using BAC clones from the mouse C57BL/6J RPCI-23 and human RPCI-11 BAC libraries and will be transfected into the Taconic Biosciences C57BL/6N Tac ES cell line.
• Homologous recombinant clones were isolated using double positive (NeoR and PuroR) and negative (Thymidine kinase - Tk) selections.
• The humanized allele is obtained after Flp-mediated removal of the selection markers. The human ATP7B gene will be expressed under the control of the endogenous mouse Atp7b promoter and should thus recapitulate the expression pattern of the mouse Atp7b gene. Replacement of the mouse Atp7b gene with its human counterpart results in loss of function of the mouse Atp7b gene.

Availability

Cryopreserved at Taconic.

Origin

The Atp7b HU model was originally created by Taconic Biosciences.

Source: Taconic Biosciences