Transgenic animals and recombinant host cells comprising specific gene variants and methods of creating same

A transgenic animal comprising at least one bluebuck (Hippotragus leucophaeus) gene variant associated with gray/blue coat color selected from the group consisting of:

• (a) a loss-of-function agouti signaling protein (ASIP) variant;
• (b) a defensin beta 103 (DEFB103) missense variant;
• (c) a loss-of-function melanophilin (MLPH) variant;
• (d) a premelanosome protein (PMEL) missense variant;
• (e) a loss-of-function lysosomal trafficking regulator (LYST) variant;
• and/or
• (f) a loss-of-function solute carrier family 45 member 2 (SLC45A2) variant.

A recombinant host cell comprising at least one bluebuck (Hippotragus leucophaeus) gene variant associated with gray/blue coat color selected from:

• (a) a loss-of-function agouti signaling protein (ASIP) variant;
• (b) a defensin beta 103 (DEFB103) missense variant;
• (c) a loss-of-function melanophilin (MLPH) variant;
• (d) a premelanosome protein (PMEL) missense variant;
• (e) a loss-of-function lysosomal trafficking regulator (LYST) variant;
• and/or
• (f) a loss-of-function solute carrier family 45 member 2 (SLC45A2) variant.

A method of creating a transgenic animal with gray/blue coat color and/or an altered melanin biosynthesis pathway of a bluebuck and/or an altered facial pattern of a bluebuck, the method comprising:

• (a) obtaining a cell from the animal;
• (b) introducing into the cell at least one bluebuck (Hippotragus leucophaeus) gene variant associated with gray/blue coat color and/or melanogenesis, wherein the one or more bluebuck gene variants associated with gray/blue coat color are selected from an ABCB6 variant, an ACE2 variant, an AP3B1 variant, an AP3D1 variant, an ASIP variant, an ATP7A variant, a BCL2 variant, a BLOC1S2 variant, a BLOC1S3 variant, a BLOC1S4 variant, a BLOC1S5 variant, a BRAF variant, a DCT variant, a DCTN1 variant, a DCTN2 variant, a DOCK7 variant, a DSTYK variant, a DTNBP1 variant, an EED variant, a FIG. 4 variant, a GGT1 variant, a GPR143 variant, a HPS1 variant, a HPS3 variant, a HPS4 variant, a HPS5 variant, a HPS6 variant, a LYST variant, a MBTPS1 variant, a MCOLN3 variant, a MFSD12 variant, a MITF variant, a MKLN1 variant, a MLANA variant, a MLPH variant, a MREG variant, a MYO5A variant, a NOTCH1 variant, a NOTCH2 variant, an OCA2 variant, a PAH variant, a PIKFYVE variant, a PMEL variant, a RAB27A variant, a RAB38 variant, a RABGGTA variant, a RAF1 variant, a SLC24A5 variant, a SLC45A2 variant, a SLC7A11 variant, a SNAI2 variant, a SPAG9 variant, a TPCN2 variant, a TYR variant, a TYRP1 variant, a VAC14 variant, a VPS33A variant, and a YKT6 variant, and the one or more bluebuck gene variants associated with melanogenesis are selected from an AP3D1 variant, an ASCC2 variant, an ATP6V0A2 variant, a CCDC53 variant, a CD72 variant, a CDK12 variant, a CHD8 variant, a COMMD5 variant, a DSCR3 variant, an EP300 variant, a FIG. 4 variant, a FRYL variant, a HDAC4 variant, a HNRNPA2B1L1 variant, a HNRNPA2B1L2 variant, a HNRNPA2B1L3 variant, a HNRNPA2B1L4 variant, a HPS3 variant, a HPS4 variant, a HPS5 variant, a HPS6 variant, an INTS8 variant, a LYST variant, a NCOR1 variant, a RAB9A variant, a RB1 variant, a SCAF4 variant, a SEC31A variant, a SIAH1 variant, a SMG7 variant, a SNX13L1 variant, a SLX13L2 variant, a TBC1D5 variant, and a WDFY1 variant;
• and/or the bluebuck gene variant associated with altered facial pattern selected from an ADAMTS20 variant, a BMP4 variant, a DOCK7 variant, an EDN3 variant, an EDNRB variant, an ETS1L1 variant, an ETS1L2 variant, a FOXD3 variant, a HDAC1 variant, an IRF1 variant, a KIT variant, a KITLG variant, a MCOLN3 variant, a MITF variant, a PAX3 variant, a SNAI2 variant, a SOX10 variant, a SOX2 variant, a TRPM1 variant, a WNT3A variant, and a ZFHX4 variant;
• and
• (c) utilizing the recombinant cell to produce a transgenic animal,
• wherein the transgenic animal has a gray/blue coat color and/or an altered melanin biosynthesis pathway of a bluebuck and/or an altered facial pattern of a bluebuck.

A method of creating a transgenic animal with gray/blue coat color, the method comprising:

• (a) obtaining a cell from the animal;
• (b) introducing into the cell at least one bluebuck gene variant associated with gray/blue coat color selected from:
• (1) a loss-of-function agouti signaling protein (ASIP) variant;
• (2) a defensin beta 103 (DEFB103) missense variant;
• (3) a loss-of-function melanophilin (MLPH) variant;
• (4) a premelanosome protein (PMEL) missense variant;
• (5) a loss-of-function lysosomal trafficking regulator (LYST) variant;
• and/or
• (6) a loss-of-function solute carrier family 45 member 2 (SLC45A2) variant, whereby introducing the at least one bluebuck gene variant produces a recombinant cell;
• and
• (c) utilizing the recombinant cell to produce a transgenic animal,
• wherein the transgenic animal has a gray/blue coat color.