Genetically modified non-human animal with human or chimeric TFR1
View Patent ↗Provided are genetically modified non-human animals that express a human or chimeric (e.g., humanized) TFR1, and methods of use thereof.
1 . A genetically-modified, non-human animal whose genome comprises at least one chromosome comprising a sequence encoding a chimeric TFR1 (Transferrin Receptor Protein 1), wherein the sequence encoding the chimeric TFR1 is operably linked to an endogenous TFR1 gene's regulatory element in the at least one chromosome; wherein the chimeric TFR1 comprises the extracellular region of human TFR1 and the cytoplasmic region of endogenous TFR1; wherein the animal detectably expresses the chimeric TFR1 on the surface of one or more cells.
2 . The animal of claim 1 , wherein the chimeric TFR1 comprises an amino acid sequence that is at least 90% identical to the sequence set forth by SEQ ID NO: 9.
3 . The animal of claim 1 , wherein the chimeric TFR1 comprises an amino acid sequence that is at least 75% identical to amino acids 89-760 of the sequence set forth by SEQ ID NO: 2.
4 . The animal of claim 1 , wherein the animal is a rodent.
5 . The animal of claim 1 , wherein the animal is a mouse.
6 . The animal of claim 1 , wherein the animal does not express endogenous TFR1 or expresses a decreased level of endogenous TFR1.
7 . A genetically-modified, non-human animal whose genome comprises a replacement of a portion of an endogenous TFR1 gene encoding the extracellular region of endogenous TFR1 with the corresponding human nucleic acid sequence encoding the extracellular region of human TFR1; wherein the animal detectably expresses a chimeric TFR1 on the surface of one or more cells.
8 . The animal of claim 7 , wherein the extracellular region of the chimeric TFR1 comprises a sequence that is at least 90% identical to the extracellular region of human TFR1.
9 . The animal of claim 7 , wherein the animal is heterozygous or homozygous with respect to the replacement of the portion of the endogenous TFR1 gene at the animal's genome.
10 . A method for making a genetically-modified, non-human animal, comprising: replacing in the genome of the animal, the portion of an endogenous TFR1 gene encoding the extracellular region of endogenous TFR1 with the corresponding human nucleic acid sequence encoding the extracellular region of human TFR1.
11 . The method of claim 10 , wherein the corresponding human nucleic acid sequence comprises a portion of exon 4 , exon 5 , exon 6 , exon 7 , exon 8 , exon 9 , exon 10 , exon 11 , exon 12 , exon 13 , exon 14 , exon 15 , exon 16 , exon 17 , exon 18 , and a portion of exon 19 , of a human TFR 1 gene.
12 . The animal of claim 1 , wherein the chimeric TFR1 comprises an amino acid sequence that is at least 95% identical to the sequence set forth by SEQ ID NO: 9.
13 . The animal of claim 1 , wherein the chimeric TFR1 comprises an amino acid sequence that is at least 90% identical to amino acids 89-760 of the sequence set forth by SEQ ID NO: 2.