Comparative Pathology: Mouse Models of Uterine Leiomyomas

Mouse models for study of human uterine leiomomas are not numerous.  In fact, some researchers wonder if any good mouse model for this benign tumor is available.  This is unfortunate since this entity is a common cause of morbidity in the female as well as use of a considerable amount of medical dollars. However, several models have recently been reported in the literature. In 1996 six transgenic lines were established by SV40-T antigen using Calbindin-D9K (CaBP9K) and either -1000 or -117 bp of regulatory sequences.    A study in the Am J Gynecology in 2008 reported a novel model in which human fibroid tumor tissue was transfected with both adenoviral cyclo-oxygenase2 and adenoviral vascular endothelial growth factor A. These tissues grew for up to 30 days following SC implantation into SCID mice.  The tumors exhibited the same phenotypic pattern as did the implant. In 2009 a report in Biology of Reproduction described production of another possible mouse model. It was developed by using a constitutively activated beta-catenin in uterine mesenchyme. It was driven by expression of Cre recombinase knocked into the Mullerian-inhibiting substance type 11 receptor promoter locus.  The mice exhibited myometrial hyperplasia and mesenchymal tumors. The resulting masses exhibited histological and molecular characteristics of human leiomyomas.  A report in 2010 described a xenograft model in which human uterine leiomyoma pieces were transplanted SC into the flanks of NOD/SCID/gamma c-null (NSG) mice.  Estrogen supplements were needed to maintain the phenotypic features of the leiomyoma.

 

UTERINE LEIOMYOMA (Mouse)

 

Click here to see the whole slide image.

Click here to view the human pathology.

 

 

References:

“MED12, the Mediator Complex Subunit 12 Gene, is Mutated at High Frequency in Uterine Leiomyomas”.  Makinen, N. et al. (2011).  Sciencedoi:10.1126/science.1208930PMID 21868628.

Rein, MS (2000). “Advances in uterine leiomyoma research: the progesterone hypothesis”. Environmental health perspectives 108 Suppl 5: 791–3. PMID 11035984.

Maruo, T.; Ohara, N.; Wang, J.; Matsuo, H. (2004). “Sex steroidal regulation of uterine leiomyoma growth and apoptosis”. Human reproduction update 10 (3): 207–220. doi:10.1093/humupd/dmh019PMID 15140868

Estradiol-dependent uterine leiomyomas in transgenic mice. Romagnolo, B, et al. J Clin Invest. 1996;98(3):777–784.   doi:10.1172/JCI118850.

Memy 1: a novel murine model for uterine leiomyoma using adenovirus-enhanced human fibroid explants in severe combined immune deficiency mice. Am J Obstet Gynecol. 2008 Aug;199(2):156.e1-8. Epub 2008 May 12 Hassan MH et al.

Constitutive Activation of Beta-Catenin in Uterine Stroma and Smooth Muscle Leads to Development of Mesenchymal Tumors in Mice.  Tanwar P.S. et al,  Biol of Reprod 81, 545-552 (2009). DOI 10.1095/biolreprod.108.075648

Establishment of a Novel Xenograft Model for Human Uterine Leiomyoma in Immunodeficient Mice.  Tsuiji, K. et al.  Tohoku Journal of Experimental Medicine. 222: pp55-61 (2010).

 

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