Jax Labs eBook - 29

IMPACTFUL SOLUTIONS CREATE INNOVATIVE SCIENCE

therapeutic can up-regulate the translation of the frataxin
protein blocked by the repeat expansion (Figure 1). These models
were selected from naturally-occurring repeat expansions in the
Tg(FXN)YG8Pook/2J mouse colony.
Two other recent in vivo models are especially beneficial
to test gene or protein replacement therapeutics. They were
created at The Jackson Laboratory to facilitate their broad
distribution to the FA scientific community. In both models, exon
2 of the murine frataxin gene was floxed using CRISPR/Cas9
endonuclease-mediated genome editing in addition to a global
null fxn allele. The conditional allele in combination with the null

allele can be used to assess frataxin depletion in the presence of
tissue-specific cre lines. These models are functionally similar
to the original mouse model published by Helene Puccio's Lab
(Puccio et al., 2001), but were re-engineered by The Jackson
Laboratory to facilitate broad distribution to the scientific
community.
In the cardiac-specific conditional model B6.Cg-Fxnem2Lutzy
Fxnem2.1Lutzy Tg(Ckmm-cre)5Khn/J (029720), the genotype of
the Fxn flox/null :: Mck-Cre mice is compound heterozygous at
the frataxin locus for the conditional and the null allele and
hemizygous carrier for the cre transgene. The highlights of this

Figure 2. Cardiac Specific Conditional Model Body Weight and Survival
Conditional ablation of frataxin in cardiac tissue using a novel floxed allele generates
Figure 1. Allelic Series in the YG8SR human containing YAC

a mutant with robust cardiac phenotype. A) Tg-Ckmm-cre cKO mutants and wildtype

Current YG8SR colony is over 1000 repeats.

controls were monitored weekly for body weight. Mutants exhibited peak body weight
between 7-8 weeks of age with weight loss requiring euthanasia by 10.5 weeks of
age. B) Tg-Ckmm-cre cKO mutants demonstrated a mean survival of 86.5 days (n=13
mutants mixed genders).

29 | GENengnews.com


https://www.ncbi.nlm.nih.gov/pubmed/?term=11175786 https://www.jax.org/strain/029720 http://www.GENengnews.com

Jax Labs eBook

Table of Contents for the Digital Edition of Jax Labs eBook

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