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A Q/ ?4 k; K) t8 T7 X: x. A
Animals capable of regenerating multiple tissue types, organs, and C1 G+ [$ m" t5 D2 ?
appendages after injury are common yet sporadic and include
, b: _/ f; Q6 @4 n/ e, D! Jsome sponge, hydra, planarian, and salamander (i.e., newt and3 {! X, E0 O' _. z; r3 M
axolotl) species, but notably such regenerative capacity is rare in: h9 D% d+ s b+ {) q* U4 s
mammals. The adult MRL mouse strain is a rare exception to the
9 a8 j4 F ] R" W- x2 W* Lrule that mammals do not regenerate appendage tissue. Certain
# D& a' A5 M( K/ v6 N# s6 Q3 Ecommonalities, such as blastema formation and basement mem-
7 s/ F% L, C+ e, Z* {7 I1 _brane breakdown at the wound site, suggest that MRL mice may" s9 |$ k, L2 U! a: q; O+ X
share other features with classical regenerators. As reported here,
% k4 G2 ~8 M) B1 a, C8 F7 NMRL fibroblast-like cells have a distinct cell-cycle (G2/M accumu-% w" n$ \3 l( q5 ]0 x9 \" X" y
lation) phenotype and a heightened basal and wound site DNA7 K% i& E2 } E6 ]( C" z. o
damage/repair response that is also common to classical regener-
+ u6 g# G1 g' Mators and mammalian embryonic stem cells. Additionally, a neutral2 U% s5 g+ F" Y" _) b' W& Z
and alkaline comet assay displayed a persistent level of intrinsic
; ?/ M- s, ]. G6 [ eDNA damage in cells derived from the MRL mouse. Similar to( e) ?# b! m5 N
mouse ES cells, the p53-target p21 was not expressed in MRL ear1 Z# F6 ]9 g4 j4 E2 O/ g; @/ V4 m
fibroblasts. Because the p53/p21 axis plays a central role in the
, q P$ H, u1 f: x+ L" f2 kDNA damage response and cell cycle control, we directly tested0 m; V% P" x; w9 j5 X5 Q: _
the hypothesis that p21 down-regulation could functionally induce
; Q3 l8 O& Z% M+ ]- O/ o% a+ d& ra regenerative response in an appendage of an otherwise non-
6 `/ u* i9 Y) \4 ]regenerating mouse strain. Using the ear hole closure phenotype,) P. Y- j/ h; X0 e/ D+ D- \: u: ]
a genetically mapped and reliable quantitative indicator of
, R9 k1 N$ R1 y5 oregeneration in the MRL mouse, we show that the unrelated
_4 I+ O, i T9 L5 P# {) O9 d% ICdkn1atmi/Tyj
0 Q: w4 m( C0 [* {. |& w/J p21−/− mouse (unlike the B6129SF2/J WT control)1 J. n! H% {9 d# _7 I1 o1 W
closes ear holes similar to MRL mice, providing a firm link between
: U" R+ ~4 T0 Hcell cycle checkpoint control and tissue regeneration. |
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发表于 2010-3-17 06:59
发表于 2010-3-17 09:21
