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cancer sites, and kallikrein-4 is capable of activating human meprins with a
preference for meprin
activation (Becker et al. 2003 ; Becker-Pauly et al. 2007 ).
b
4.4 Disruption of the Meprin Genes in Mice
In an effort to investigate in vivo functions of meprins, meprins
a
and
b
null mice
(
KO) were generated by targeted disruption of the mouse genes (Norman
et al. 2003a ; Banerjee et al. 2009 ). Meprin double KO (dKO) mice have also been
established (Sun et al. 2009 ). The KO mice generally do not exhibit any gross
pathological phenotype, with normal histological structures of the kidney and
intestine where meprins are abundantly expressed. The litter numbers are somewhat
smaller than the wild type, but growth, development, and fertility are normal.
However, in response to different challenges, the meprin KO mice exhibited a
variety of abnormalities. For example, meprin
a
KO and
b
KO mice are less vulnerable to
kidney damage in the model of ARF induced by surgical ischemia and reperfusion
(Fig. 4.6 ). Renal ischemia/reperfusion results in extensive redistribution of hetero-
meric meprin A in the mouse C57BL/6 mouse kidney, and the lack of the mem-
brane-bound meprins in the
b
KO results in much less damage to the kidney
b
Fig. 4.6 Kidney damage in
mice deficient in meprin
b
and wild-type mice after
ischemia and reperfusion.
Blood urea nitrogen (BUN; a)
and plasma creatinine levels
(b) following renal ischemia/
reperfusion ( I / R ) in wild-type
(WT) and meprin (Mep)
b
knockout (KO) mice. Male
WT and meprin b KO C57BL/
6 129 F2 mice, 8-10 weeks
old, were subjected to 26 min
of warm renal ischemia
followed by up to 72 h of
reperfusion. ( filled square )
WT mice; ( filled triangle )
meprin b KO mice. Values are
means
13-14 and
6-7 for each group in a and b,
respectively. * p
SE; n
ΒΌ
0.02;
<
** p
0.001
(Student's t test) (Bylander
et al. 2008 )
0.01; *** p
<
<
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