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
This is substantiated by the observation that, similarly to some types of SGR that affect the RNA decay machinery (for example, DIS3 or MTREX; Fig. 4c) and likely increase the level of functional hTR, an inhibitor of the hTR poly(A) polymerase PAPD5 increases the level of mature hTR and improves the potential of haematopoietic stem and progenitor cells in the context of PARN or dyskerin deficiency59,237,238,239.
potential gene therapy targets to increase TERC (hTR)
Nonsense-mediated mRNA decay efficiency influencesbleeding severity inITGA2Bc.2659C > T (p.Q887X)knock-in mice
PMID: 33928629
Previously annotated and reported Probands: PMID: 29675921. New Functional Evidence.
CAID: CA8602626
Gene: ITGA2B
Variant: NM_000419.3:c.2671C>T (p.Gln891Ter)
FunctionalEvidence: For Q887X mutation: Knock-in mice generated using CRISPR/Cas9 displaed no spontaneous bleeding phenotypes. Platelet morphology cofirmed to be normal and comparable platelet numbers to WT mice. Mean bleeding time increased and platelet aggregation impaired compared to WT. ITGA2B mRNA levels low in KI mice.
Impact of mutations in the von Willebrand factor A2 domain on ADAMTS13-dependent proteolysis
PMID 16322474
Notes Recombinant full length p.Ile1628Thr expressed in HEK293 and purified from growth media was NOT digested by recombinant ADAMTS13 in non-denaturing conditions (Table 1, Fig 5a). However, the the A1-A3 p.Ile1628Thr truncations were digested by ADAMTS13 in non-denaturing conditions while WT recombinant VWF truncations were not (Fig 6).
Functional Consequences of Hypertrophic and Dilated Cardiomyopathy-causing Mutations in α-Tropomyosin*
PMID: PMID:16043485
Gene: TPM1
Disease: hypertrophic cardiomyopathy 3
MonDO: MONDO:0007267
InheritancePattern: AD