Proteinuria-Induced Chronic Kidney Disease in the ICGN/Oa Mice with a Mutation of Tensin2 Gene

Figures & data

Figure 1. PCR analysis of the ICGN/Oa mice for the tensin2 locus. The DNA extracted from the wild-type (lane 1), heterozygous (lane 2), and homozygous (lane 3) mice were genotyped using a single pair of specific primers for the wild-type and mutant alleles, respectively. Lane M was loaded with the size marker.

Figure 2. Effects of a tensin2 mutation on body and kidney weights of the heterozygous and homozygous mice at 5, 15, and 25 weeks of age compared with the wild-types. (A) body and (B) kidney weights. These parameters are expressed as mean ± SD. *p < 0.05, ***p < 0.001 as compared with the wild-types.

Figure 3. SDS-PAGE analysis of urine from the three strains of ICGN/Oa mice at 5, 15, and 25 weeks of age.

Table 1 Effects of a tensin2 mutation on urine and serum biochemical parameters in the heterozygous and homozygous mice at 5, 15, and 25 weeks of age compared with the wild-types

	(+/+)	(nep/+)	(nep/nep)
uAlb (mg/ml)
5W	1.15 ± 0.36	1.04 ± 0.70	10.64 ± 7.09^‡
15W	1.71 ± 0.90	1.48 ± 0.87	21.98 ± 6.88 ^‡
25W	1.27 ± 0.68	1.31 ± 1.02	8.19 ± 4.61^‡
uAlb (g/kg/24h)
5W	0.06 ± 0.01	0.07 ± 0.01	1.69 ± 0.59^‡
15W	0.10 ± 0.03	0.05 ± 0.01	2.09 ± 0.30^‡
25W	0.04 ± 0.01	0.03 ± 0.01	2.16 ± 0.64^‡
sAlb (mg/ml)
5W	32.1 ± 2.6	32.7 ± 2.4	23.4 ± 4.0^‡
15W	31.6 ± 4.1	31.7 ± 3.5	22.1 ± 2.8^‡
25W	29.4 ± 2.2	31.3 ± 3.2	23.0 ± 1.9^‡
sTcho (%)
5W	1	1.01 ± 0.08	1.40 ± 0.17^‡
15W	1.03 ± 0.16	1.03 ± 0.09	1.76 ± 0.25^‡
25W	1.03 ± 0.22	0.95 ± 0.16	1.99 ± 0.30^‡
BUN (mg/dl)
5W	22.0 ± 3.7	19.6 ± 3.2	22.2 ± 3.2
15W	19.7 ± 3.7	20.0 ± 3.2	41.2 ± 17.9^†
25W	18.5 ± 1.3	19.3 ± 3.2	101.7 ± 45.9^‡
sCre (mg/dl)
5W	0.63 ± 0.09	0.66 ± 0.03	0.62 ± 0.09
15W	0.59 ± 0.07	0.62 ± 0.07	0.83 ± 0.24
25W	0.61 ± 0.09	0.53 ± 0.04	1.62 ± 0.62^‡

*p < 0.05, ^†p < 0.01, ^‡p < 0.001.

Abbreviations: uAlb = urinary albumin, sAlb = serum albumin, sTcho = serum total cholesterol, BUN = blood urea nitrogen, sCre = serum creatinine. These parameters are expressed as mean ± SD.

Figure 4. Histopathology of the renal cortex in the ICGN/Oa mice. Representative photographs of renal arteries at 5 weeks of the (A) wild-types, (B) heterozygotes, and (C) homozygotes, and at 25 weeks of the (D) wild-types, (E) heterozygotes, and (F) homozygotes. (G) Semiquantification of these histological findings. Mononuclear cell infiltration indexes are expressed as mean ± SD. *p < 0.05, ***p < 0.001 as compared with the wild-types. Representative photomicrographs of renal tubules at 5 weeks of the (H) wild-types, (I) heterozygotes, and (J) homozygotes, and at 25 weeks of the (K) wild-types, (L) heterozygotes, and (M) homozygotes. (N) Semiquantification of these histological findings. Tubular injury indexes are expressed as mean ± SD.

Figure 5. Time courses of the expression of α-SMA and type I collagen in the ICGN/Oa mice. Representative photomicrographs of α-SMA immunostain at 5 weeks of the (A) wild-types and (B) homozygotes, 15 weeks of the (C) wild-types and (D) homozygotes, and 25 weeks of the (E) wild-types and (F) homozygotes. (G) Semiquantification of these histological findings. Matrix scores for α‐SMA are expressed as mean ± SD. Representative photomicrographs of type I collagen immunostain at 5 weeks of the (H) wild-types and (I) homozygotes, 15 weeks of the (J) wild-types and (K) homozygotes, and 25 weeks of the (L) wild-types and (M) homozygotes. (N) Semiquantification of these histological findings. Matrix scores for type I collagen are expressed as mean ± SD. **p < 0.01, ***p < 0.001 as compared with the wild-types.

Figure 6. Time courses of the proliferating and apoptotic TECs in the ICGN/Oa mice. Representative photomicrographs of PCNA immunostain at 5 weeks of the (A) wild-types and (B) homozygotes, 15 weeks of the (C) wild-types and (D) homozygotes, and 25 weeks of the (E) wild-types and (F) homozygotes. (G) Semiquantification of these histological findings. The numbers of PCNA-positive TECs are expressed as mean ± SD. Representative photomicrographs of TUNEL at 5 weeks of the (H) wild-types and (I) homozygotes, 15 weeks of the (J) wild-types and (K) homozygotes, and 25 weeks of the (L) wild-types and (M) homozygotes. (N) Semiquantification of these histological findings. The numbers of TUNEL-positive TECs are expressed as mean ± SD. *p < 0.05, **p < 0.01 as compared with the wild-types.