Animal models for Niemann-Pick type C: implications for drug discovery & development

Figures & data

Table 1. Feline and murine NPC models.

Species	Name	Affected Gene	Mutation (cDNA position)	Mutation outcome	Strain of origin	References
Feline	NPC1	Npc1	c.2864G>C	p.Cys955Ser (C955S)	N.A.	[38,39]
Feline	NPC2	Npc2	c.82 + 5G>A	p.Gly28_Ser29ins35 (G28_S29ins35) (retention of 105 bp in the mature mRNA leading to an in-frame insertion of 35 amino acids between residues 28 and 29 of NPC2 protein	N.A.	[45]
Murine	Npc1^nih (Npc1^m1n)	Npc1	824 bp of MaLR retrotransposon-like DNA replacing 703 bp of wild-type genomic sequence.	Frameshift + premature stop codon (null allele)	BALB/c	[46–48]
Murine	Npc1^spm	Npc1	c.2911 + 3A>C	p.Val971GlyfsTer31 (V971GfsTer31) (cDNA retains 43 base pairs of intron 19 shifting the reading frame, replacing p.Val 971 for a Gly, adding 30 novel residues followed by a stop codon)	C57BL/Ks	[49,72]
Murine	Npc1^pf/pf	Npc1	c.604C>G; c.607-608TT>GC	p.Pro202Ala;Phe203Ala (P202A/F203A)	C57BL/6	[76]
Murine	Npc1^nmf164	Npc1	c.3163A>G	p.Asp1005Gly (D1005G)	C57BL/6	[49]
Murine	Npc1^tm(I1064T)Dso (Npc1^I1061T)	Npc1	c.3179T>C+ loxP sites flanking exons 14–20	p.Ile1064Thr (I1064T)	C57BL/6	[70]
Murine	Npc1^imagine	Npc1	c.1554-1009G>A	Inclusion of 194-bp pseudoexon in intron 9 resulting in a premature stop codon	C57BL/6	[83]
Murine	Npc1^pioneer	Npc1	c.1920delG	p.His641ThrfsTer2 (H641TfsTer2) (frameshift replacing p.His641 with Thr and resulting in a premature stop codon two residues downstream)	C57BL/6	[83]
Murine	Npc2^tm1Plob	Npc2	Insertion into intron 2 resulting in splice junction mutation	Hypomorhic allele (decrease in correctly spliced Npc2 mRNA)	BALB/c (or mixed)	[73]
Murine	Npc1 ASO	Npc1	N/A	Antisense-mediated knockdown of hepatic Npc1	BALB/c	[79]

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