Biology Reference
In-Depth Information
Table 9.2 Major phenotypes of elastase null-mutant mice
Genotype
Phenotype
Reference
NE
/
Reduced bacterial killing
Belaaouaj et al. (
1998
),
Weinrauch et al. (
2002
)
Liu et al. (
2000
)
Shapiro et al. (
2003
)
Protection from bullous pemphigoid
Partial protection from cigarette
smoke-induced emphysema
Decreased lung tumor growth
Houghton et al. (
2010
)
CG
/
Normal neutrophil function
Impaired PMN integrin clustering
MacIvor et al. (
1999
)
Raptis et al. (
2005
)
a
PR3
/
Decreased neutrophilic inflammation
Kessenbrock et al. (
2008
)
MMP2
/
Protected from AAA formation
Decreased tumor growth
Longo et al. (
2002
)
Itoh et al. (
1998
)
MMP3
/
Protected from AAA formation
Silence et al. (
2001
)
MMP7
/
Impaired intestinal clearance of bacteria
Impaired neutrophil recruitment to lung
Decreased tumor growth
Wilson et al. (
1999
)
Li et al. (
2002
)
Wilson et al. (
1997
)
MMP9
/
Abnormal bone development
Protected from AAA formation
Decreased tumor growth
Vu et al. (
1998
)
Pyo et al. (
2000
)
Bergers et al. (
2000
),
Coussens et al. (
2000
)
Liu et al. (
1998
)
Protection from bullous pemphigoid
MMP10
/
Normal adipose tissue development
Lijnen et al. (
2009
)
MMP12
/
Impaired basement membrane penetration
by macrophages
Protection from cigarette smoke-induced
emphysema
Protection from cigarette smoke-induced
macrophage accumulation
Normal response to AAA formation
Partial protection from AAA formation
Increased susceptibility to lung metastases
Reduced bacterial killing
Shipley et al. (
1996
)
Hautamaki et al. (
1997
)
Houghton et al. (
2006a
,
b
)
Pyo et al. (
2000
)
Longo et al. (
2005
)
Houghton et al. (2006)
Houghton et al. (
2009
)
Cat S
/
Impaired antigen presentation
Protection from arthritis
Protection from atherosclerosis
Shi et al. (
1999
)
Nakagawa et al. (
1999
)
Sukhova et al. (
2003
)
Cat L
/
Impaired skin and hair follicle development
Roth et al. (
2000
)
Cat K
/
Osteopetrosis
Protection from atherosclerosis
Saftig et al. (
1998
)
Lutgens et al. (
2006
)
a
This description is of an NE/PR3 doubly deficient mouse. The
PR3
/
single mutant null mouse
has not been described
intracellular enzymes predominantly located within endosomes and lysosomes.
They are occasionally secreted into the extracellular space. Four of these enzymes
are capable of degrading elastin, cathepsin V, S, L, and K.
Hydrolysis of elastic fibers and other components of the ECM likely occur via
both extracellular and intracellular means. Partially degraded collagen fragments,
for example, are trafficked to lysosomes where they are further degraded by the
intracellular cysteine cathepsins. Elastic fiber degradation by cysteine cathepsins
displays a “team” approach, whereby cathepsin K attacks insoluble fibers, and
cathepsins S and K prefer soluble fragments.
