mice have short life spans (~2–3 years), residual Tert expression in many adult tissues (discussed below)8, and, in the common Mus musculus laboratory strain, long telomeres (~20–65 kb)9
Mouse models should potentially be downgraded given the significant difference in telomere biology
Generation of a rat model of MPSIVA disease
NonHumanModel: Mus musculus
GeneAlteration: p.Arg386Cys the most frequently reported missense variant linked as a causal pathogenic allele in mucopolysaccharidosis IVA patients
ModelPhenotype: In addition to undetectable GALNS enzyme activity in any assayed tissue, increased keratan sulfate detection in liver tissue and blood serum, the boney deformations missing from previous models were present in this mouse model HP:0004325, MP:0001258, HP:0005736
HumanPhenotype: HP:4000197, HP:0012069, HP:0004322, HP:0005736
ModelEvidence: CRISPR/Cas9 directed site mutagenesis of murine Galns coding sequence at codon homologous to the human p.Arg388Cys mutation cited in human MPSIVA patients. Mouse model showed increased keratan sulfate accumulation in liver and blood serum, undetectable n-acetylgalactosamine-6-sulfatase activity in any body tissue assayed as well as skeletal deformities consistent with human MPSIVA patients
ModelVariant: p.Arg388Cys
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