MCWHIRTER, John,MACDONALD, Lynn,STEVENS, Sean,DAVIS, Samuel,BUCKLER, David,HOSIAWA, Karolina,MURPHY, Andrew
申请号：
ES12746246
公开号：
ES2758051T3
申请日:
2012.08.03
申请国别(地区):
ES
年份:
2020
代理人:
摘要：
A mouse whose genome comprises: (a) a humanized immunoglobulin heavy chain variable locus comprising at least one unreordered human VH segment, at least one unreordered human DH, and at least one unreordered human JH operably linked to a gene endogenous heavy chain constant region； (b) a humanized immunoglobulin light chain variable locus comprising not more than one, or not more than two, rearranged human light chain V / J sequences operably linked to an endogenous light chain constant region gene； and, (c) an ectopic nucleic acid sequence expressing a functional mouse ADAM6a protein or a functional ortholog or a functional homolog or a functional fragment thereof and an ectopic nucleic acid sequence expressing a functional mouse ADAM6b protein or a functional ortholog or functional homolog or a functional fragment thereof, the ADAM6 proteins, orthologs, homologs or fragments being functional in a male mouse, wherein said function is associated with male fertility, said mouse having the function of endogenous ADAM6 eliminated or reduced, and further characterized by its germline lacking a non-rearranged endogenous immunoglobulin Vκ gene segment and a non-rearranged endogenous immunoglobulin Jκ gene segment.Un ratón cuyo genoma comprende: (a) un locus variable de cadena pesada de inmunoglobulina humanizada que comprende al menos un segmento VH humano no reordenado, al menos un DH humano no reordenado, y al menos un JH humano no reordenado unidos operativamente a un gen de región constante de cadena pesada endógeno； (b) un locus variable de cadena ligera de inmunoglobulina humanizada que comprende no más de una, o no más de dos, secuencias V/J de cadena ligera humana reordenadas unido operativamente a un gen de región constante de cadena ligera endógeno； y, (c) una secuencia de ácido nucleico ectópico que expresa una proteína ADAM6a de ratón funcional o un ortólogo funcional o un homólogo funcional o un fragmento funcional de la misma y una secuencia de ácido nucleic
