Macdonald, Lynn,Murphy, Andrew,Mcwhirter, John,Martin, Joel
申请号:
NZ71250813
公开号:
NZ712508A
申请日:
2013.03.15
申请国别(地区):
NZ
年份:
2018
代理人:
摘要:
Disclosed is a method of obtaining a cell, comprising harvesting a lymphocyte from a non-human animal; wherein the non-human animal comprises in its germline genome either or both (i) an unrearranged immunoglobulin heavy chain variable region gene sequence comprising a substitution of at least one non-histidine codon with a histidine codon or an insertion of at least one histidine codon, wherein the substituted or inserted histidine codon is not encoded by a corresponding wild-type heavy chain variable region gene segment, and (ii) an unrearranged immunoglobulin light chain variable region gene sequence comprising a substitution of at least one non-histidine codon with a histidine codon or an insertion of at least one histidine codon, wherein the substituted or inserted histidine codon is not encoded by a corresponding wild-type light chain variable region gene segment. Also disclosed are methods for making non-human animals comprising: modifying the non-human animal in its germline to comprise either or both (i) at an endogenous non-human immunoglobulin heavy chain locus an unrearranged immunoglobulin heavy chain variable region gene sequence comprising in a CDR3 encoding sequence a substitution of at least one non-histidine codon with a histidine codon or an insertion of at least one histidine codon, and (ii) at an endogenous non-human immunoglobulin light chain locus a rearranged immunoglobulin light chain variable region gene sequence comprising in a CDR3 encoding sequence a substitution of at least one non-histidine codon with a histidine codon or an insertion of at least one histidine codon.