| First Author | Howell MD | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 7183 |
| PubMed ID | 28775379 | Mgi Jnum | J:281591 |
| Mgi Id | MGI:6379343 | Doi | 10.1038/s41598-017-07468-2 |
| Citation | Howell MD, et al. (2017) TIA1 is a gender-specific disease modifier of a mild mouse model of spinal muscular atrophy. Sci Rep 7(1):7183 |
| abstractText | Spinal muscular atrophy (SMA) is caused by deletions or mutations of Survival Motor Neuron 1 (SMN1) gene. The nearly identical SMN2 cannot compensate for SMN1 loss due to exon 7 skipping. The allele C (C (+/+)) mouse recapitulates a mild SMA-like phenotype and offers an ideal system to monitor the role of disease-modifying factors over a long time. T-cell-restricted intracellular antigen 1 (TIA1) regulates SMN exon 7 splicing. TIA1 is reported to be downregulated in obese patients, although it is not known if the effect is gender-specific. We show that female Tia1-knockout (Tia1 (-/-)) mice gain significant body weight (BW) during early postnatal development. We next examined the effect of Tia1 deletion in novel C (+/+)/Tia1 (-/-) mice. Underscoring the opposing effects of Tia1 deletion and low SMN level on BW gain, both C (+/+) and C (+/+)/Tia1 (-/-) females showed similar BW gain trajectory at all time points during our study. We observed early tail necrosis in C (+/+)/Tia1 (-/-) females but not in males. We show enhanced impairment of male reproductive organ development and exacerbation of the C (+/+)/Tia1 (-/-) testis transcriptome. Our findings implicate a protein factor as a gender-specific modifier of a mild mouse model of SMA. |
