著者
Seiya MIZUNO Saori IIJIMA Tomoko OKANO Noriko KAJIWARA Satoshi KUNITA Fumihiro SUGIYAMA Ken-ichi YAGAMI
出版者
公益社団法人 日本実験動物学会
雑誌
Experimental Animals (ISSN:13411357)
巻号頁・発行日
vol.60, no.2, pp.161-167, 2011 (Released:2011-04-21)
参考文献数
14
被引用文献数
5 18

We found 6 spontaneous mutant mice with long pelage hair in our ICR breeding colony. The abnormal trait was restricted to long hair in these mice, which we named moja. They were fertile and showed the same growth and behavior as wild-type mice. To investigate the manner of the genetic inheritance of the moja allele, offspring were bred by mating the moja mice; all offspring had long pelage hair. Furthermore, we performed a reciprocal cross between moja mice and wild-type ICR mice with normal hair. All offspring exhibited normal hair suggesting an autosomal recessive inheritance of the trait. The moja/moja hair phenotype was maintained in skin grafted onto nude mice, suggesting that circulating or diffusible humoral factors regulating the hair cycle are not involved in the abnormal trait. The phenotype of moja/moja mice is similar to that of Fgf5-deficient mice. Therefore, we examined the expression of Fgf5 by RT-PCR in moja/moja mice. As expected, no Fgf5 expression was found in moja/moja mouse skin. PCR and DNA sequence analyses were performed to investigate the structure of the Fgf5 gene. We found a deletion of a 9.3-kb region in the Fgf5 gene including exon 3 and its 5’ and 3’ flanking sequences. Interestingly, the genomic deletion site showed insertion of a 498-bp early transposon element long terminal repeat. Taken together, these results suggest that the long hair mutation of moja/moja mice is caused by disruption of Fgf5 mediated by insertion of a retrotransposon.
著者
Hidetoshi Sugihara Koichi Kimura Keitaro Yamanouchi Naomi Teramoto Tomoko Okano Masao Daimon Hiroyuki Morita Katsu Takenaka Takanori Shiga Jun Tanihata Yoshitsugu Aoki Tokiko Inoue-Nagamura Hiroshi Yotsuyanagi Issei Komuro
出版者
International Heart Journal Association
雑誌
International Heart Journal (ISSN:13492365)
巻号頁・発行日
pp.20-372, (Released:2020-11-13)
参考文献数
25
被引用文献数
9

Duchenne muscular dystrophy (DMD) is X-linked recessive myopathy caused by mutations in the dystrophin gene. Although conventional treatments have improved their prognosis, inevitable progressive cardiomyopathy is still the leading cause of death in patients with DMD. To explore novel therapeutic options, a suitable animal model with heart involvement has been warranted.We have generated a rat model with an out-of-frame mutation in the dystrophin gene using CRISPR/Cas9 genome editing (DMD rats). The aim of this study was to evaluate their cardiac functions and pathologies to provide baseline data for future experiments developing treatment options for DMD.In comparison with age-matched wild rats, 6-month-old DMD rats showed no significant differences by echocardiographic evaluations. However, 10-month-old DMD rats showed significant deterioration in left ventricular (LV) fractional shortening (P = 0.024), and in tissue Doppler peak systolic velocity (Sa) at the LV lateral wall (P = 0.041) as well as at the right ventricular (RV) free-wall (P = 0.004). These functional findings were consistent with the fibrotic distributions by histological analysis.Although the cardiac phenotype was milder than anticipated, DMD rats showed similar distributions and progression of heart involvement to those of patients with DMD. This animal may be a useful model with which to develop effective drugs and to understand the underlying mechanisms of progressive heart failure in patients with DMD.