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Scaffold attachment factor B2 (SAFB2)- mice reveal non-redundant functions of SAFB2 compared with its paralog, SAFB1.

Jiang S, Katz TA, Garee JP, DeMayo FJ, Lee AV, Oesterreich S - Dis Model Mech (2015)

Bottom Line: Scaffold attachment factors SAFB1 and SAFB2 are multifunctional proteins that share >70% sequence similarity.Further analysis showed a significantly increased testis weight in SAFB2(-/-) mice, which was associated with an increased number of Sertoli cells.Our data suggest that this is at least in part caused by alterations in androgen-receptor function and expression upon deletion of SAFB2.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

No MeSH data available.


Related in: MedlinePlus

Increased number of Sertoli cells in SAFB2−/− mice. (A) Bars represent testis weight as percent (mean±s.d.) of total body weight (BW), measured in SAFB2+/+ (n=12) and SAFB2−/− (n=22) mice. (B) Number of Sertoli cells (mean±s.d.) in SAFB2+/+ (n=4) and SAFB2−/− (n=14) mice. (C) Representative picture of IHC for Wilms tumor 1 (WT1) in SAFB2+/+ and SAFB2−/− mouse testes (scale bars: 10 μm). (D) Reporter assay in LNCaP cells (mean±s.e.m., n=4) with fold change compared to ARE alone. A two-way ANOVA with a Bonferroni post-test was used to analyze the data (*P<0.05). (E) Number of AR-positive cells/tubule (mean±s.e.m., n=6). A t-test was conducted for statistical analysis (**P<0.01).
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DMM019885F5: Increased number of Sertoli cells in SAFB2−/− mice. (A) Bars represent testis weight as percent (mean±s.d.) of total body weight (BW), measured in SAFB2+/+ (n=12) and SAFB2−/− (n=22) mice. (B) Number of Sertoli cells (mean±s.d.) in SAFB2+/+ (n=4) and SAFB2−/− (n=14) mice. (C) Representative picture of IHC for Wilms tumor 1 (WT1) in SAFB2+/+ and SAFB2−/− mouse testes (scale bars: 10 μm). (D) Reporter assay in LNCaP cells (mean±s.e.m., n=4) with fold change compared to ARE alone. A two-way ANOVA with a Bonferroni post-test was used to analyze the data (*P<0.05). (E) Number of AR-positive cells/tubule (mean±s.e.m., n=6). A t-test was conducted for statistical analysis (**P<0.01).

Mentions: Despite lack of gross phenotypes on fertility, further analysis showed that SAFB2−/− mice displayed a significant increase in testis weight compared to SAFB2+/+ mice (Fig. 5A). This was in contrast to SAFB1−/− male mice, which we had previously shown to have decreased testes size (Ivanova et al., 2005). A potential cause for increased testes size in SAFB2−/− mice were changes in Sertoli cells, known as the ‘nursing’ cells of the testes. Staining for expression of Wilms tumor 1 (WT1), a marker of Sertoli cells, showed a significantly increased number of Sertoli cells in SAFB2−/− testes compared to SAFB2+/+ testes (Fig. 5B). A representative section showing increased WT1 staining in the SAFB2−/− mice is shown in Fig. 5C. Because SAFB1 was previously shown to regulate AR activity (Mukhopadhyay et al., 2014) and AR signaling can effect numbers of Sertoli cells (Johnston et al., 2004; Tan et al., 2005), we next tested the effect of SAFB2 on androgen-stimulated AR activity in a number of cell lines (LNCaP, COS7, 239T). We observed significant repression of AR activity by SAFB2 overexpression in LNCaP (Fig. 5D) and COS7 cells, but not in 293T (data not shown). In adult mice (12 months), there was less AR expression in SAFB2−/− testes compared to SAFB2+/+ testes (Fig. 5E, and supplementary material Fig. S2), possibly as a result of negative feedback as previously described (Cai et al., 2011). There were no differences in expression of ERβ between SAFB2−/− and SAFB2+/+ testes (data not shown). Thus, SAFB2−/− mice have increased weight of testes, associated with an increase in Sertoli cell number, likely at least in part owing to altered AR signaling.Fig. 5.


Scaffold attachment factor B2 (SAFB2)- mice reveal non-redundant functions of SAFB2 compared with its paralog, SAFB1.

Jiang S, Katz TA, Garee JP, DeMayo FJ, Lee AV, Oesterreich S - Dis Model Mech (2015)

Increased number of Sertoli cells in SAFB2−/− mice. (A) Bars represent testis weight as percent (mean±s.d.) of total body weight (BW), measured in SAFB2+/+ (n=12) and SAFB2−/− (n=22) mice. (B) Number of Sertoli cells (mean±s.d.) in SAFB2+/+ (n=4) and SAFB2−/− (n=14) mice. (C) Representative picture of IHC for Wilms tumor 1 (WT1) in SAFB2+/+ and SAFB2−/− mouse testes (scale bars: 10 μm). (D) Reporter assay in LNCaP cells (mean±s.e.m., n=4) with fold change compared to ARE alone. A two-way ANOVA with a Bonferroni post-test was used to analyze the data (*P<0.05). (E) Number of AR-positive cells/tubule (mean±s.e.m., n=6). A t-test was conducted for statistical analysis (**P<0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

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DMM019885F5: Increased number of Sertoli cells in SAFB2−/− mice. (A) Bars represent testis weight as percent (mean±s.d.) of total body weight (BW), measured in SAFB2+/+ (n=12) and SAFB2−/− (n=22) mice. (B) Number of Sertoli cells (mean±s.d.) in SAFB2+/+ (n=4) and SAFB2−/− (n=14) mice. (C) Representative picture of IHC for Wilms tumor 1 (WT1) in SAFB2+/+ and SAFB2−/− mouse testes (scale bars: 10 μm). (D) Reporter assay in LNCaP cells (mean±s.e.m., n=4) with fold change compared to ARE alone. A two-way ANOVA with a Bonferroni post-test was used to analyze the data (*P<0.05). (E) Number of AR-positive cells/tubule (mean±s.e.m., n=6). A t-test was conducted for statistical analysis (**P<0.01).
Mentions: Despite lack of gross phenotypes on fertility, further analysis showed that SAFB2−/− mice displayed a significant increase in testis weight compared to SAFB2+/+ mice (Fig. 5A). This was in contrast to SAFB1−/− male mice, which we had previously shown to have decreased testes size (Ivanova et al., 2005). A potential cause for increased testes size in SAFB2−/− mice were changes in Sertoli cells, known as the ‘nursing’ cells of the testes. Staining for expression of Wilms tumor 1 (WT1), a marker of Sertoli cells, showed a significantly increased number of Sertoli cells in SAFB2−/− testes compared to SAFB2+/+ testes (Fig. 5B). A representative section showing increased WT1 staining in the SAFB2−/− mice is shown in Fig. 5C. Because SAFB1 was previously shown to regulate AR activity (Mukhopadhyay et al., 2014) and AR signaling can effect numbers of Sertoli cells (Johnston et al., 2004; Tan et al., 2005), we next tested the effect of SAFB2 on androgen-stimulated AR activity in a number of cell lines (LNCaP, COS7, 239T). We observed significant repression of AR activity by SAFB2 overexpression in LNCaP (Fig. 5D) and COS7 cells, but not in 293T (data not shown). In adult mice (12 months), there was less AR expression in SAFB2−/− testes compared to SAFB2+/+ testes (Fig. 5E, and supplementary material Fig. S2), possibly as a result of negative feedback as previously described (Cai et al., 2011). There were no differences in expression of ERβ between SAFB2−/− and SAFB2+/+ testes (data not shown). Thus, SAFB2−/− mice have increased weight of testes, associated with an increase in Sertoli cell number, likely at least in part owing to altered AR signaling.Fig. 5.

Bottom Line: Scaffold attachment factors SAFB1 and SAFB2 are multifunctional proteins that share >70% sequence similarity.Further analysis showed a significantly increased testis weight in SAFB2(-/-) mice, which was associated with an increased number of Sertoli cells.Our data suggest that this is at least in part caused by alterations in androgen-receptor function and expression upon deletion of SAFB2.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

No MeSH data available.


Related in: MedlinePlus