Searching for a treatment for Alport syndrome using mouse models

Table 1 Mouse models of Alport syndrome

Gene	Mutation	Ref.
ARAS
COL4A3	exon 48	[15]
COL4A3	exon 48-50	[16]
COL4A3-COL4A4	COL4A3 exon 2-COL4A4 exon 12	[17]
COL4A4	exon 30	[18]
XLAS
COL4A5	exon 1	[19]

ARAS: Autosomal recessive Alport syndrome; XLAS: X-linked Alport syndrome.

Table 2 The efficacy of pharmacological drugs in COL4A3 -/- mice

Drug	Survival (d)	Efficacy
Vasopeptidase inhibitor[22]	172	(+++)
ACE inhibitor[23]	150	(+++)
ARB[24]	98	(++)
HMG-CoA reductase inhibitor[26]	91	(++)
CCR1 inhibitor[27]	86	(+)
TNF-alpha antagonist[29]	81	(+)
Renin inhibitor[30]	78	(+)
Vitamin D analog[31]	75	(+)
Untreated (129SvJ background)	71

ACE: Angiotensin converting enzyme; ARB: Angiotensin-II receptor blocker; CCR1: Chemokine (CC motif) receptor 1; HMG-CoA: 3-hydroxy-3-methylglutaryl-coenzyme A; TNF: Tumor necrosis factor.

Table 3 The effects of bone marrow transplantation therapy in COL4A3 -/- mice

	Prodromidi et al[45]		Sugimot et al[46]		Katayama et al[47]
	WT -> KO	KO -> KO	WT -> KO	KO -> KO	WT -> KO	KO -> KO
α3 (IV) IF	+	-	+	-	-	-
α3 (IV) WB	no data	no data	+	-	-	-
Col4a3 mRNA	+	-	+	-	+	-
BUN and Cr	improved	no change	improved	no change	improved	improved
Renal pathology	improved	no change	improved	no change	improved	improved
Survival (d)	no data	no data	no data	no data	125	135

WT: Wild-type; KO: Knockout; IF: Immunofluorescence; WB: Western blot; BUN: Blood urea nitrogen; Cr: Creatinine.