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August 15, 2010

Ellen Heber-Katz on The MRL mouse - how it regenerates and how we might do the same

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Ellen Heber-Katz on The MRL mouse - how it regenerates and how we might do the same

We will present an overview of the current state of mammalian regeneration in the context of recent and ongoing discoveries in the MRL mouse system. The MRL mouse is the first and to date the only genetically dissectable mammalian model for regeneration and as such provides a "laboratory" for assessing theories and potential clinical approaches to achieving the medical goal of regeneration. The very recent finding that the turning off of a single gene – p21 - related to the regulation of the cell cycle can convert an otherwise non-regenerating mouse to a regenerator leads to two important conclusions. First, the molecular apparatus for regeneration has survived the long evolutionary gap between lower species such as hydra and salamander up through the advent of mammals. And second, the fact that the capacity to regenerate can be “uncloaked“ through the turning off of a single gene gives impetus to the possibility that regeneration can be induced by drug therapy alone.


Epimorphic regeneration. Newts grow back a limb in about 10 weeks. Full size takes a bit longer.

Deer antler is epimorphic regeneration as well.
In the MRL mouse it regenerates hole punches in ears within 30 days.
Normal mice do not restore ear holes. Rabbits do regenerate ear holes.

MRL mouse can also restore heart cells after heart cells are killed with cold probes.

MRL can grow back knee cartilige.

MRL mouse does not grow back limbs but grows back more of the limb. Say if you cut a finger to two joint down. MRL mouse grows back one of the joints but not the whole finger.

Other kind of metabolism.

aerobic glycolysis is used by tumors, stem cells and in the regeneration tissues.

Retained features of embryonic metabolism in the adult MRL mouse

The Scientist - The recipe for regeneration

Genes that seem to be involved in regeneration.
P21 (C1P1/WAF1) P19 (ARF) (P14 in humans) P53

Does continuous regeneration lead to immortality

MRL mouse has autoimmune disease so they do not live longer.

Fixing the autoimmunity leads to mice that lead to longer lived mouse

Need to regeneration without tumors and then it could lead to a lot longer lives.

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