A Novel Animal Model of Induced Breast Precancerous Lesion in Tree Shrew

Abstract

Chinese tree shrew, an animal exhibited closer evolutionary relationship with humans compared to rodents, is getting increasingly attentions as an appealing experimental animal model for human diseases. However, a high-efficiency and stable method to establish tree shrew breast precancerous lesions model has not been clearly elucidated. Thus, the current study aimed to explore the way of establishing breast precancerous model in tree shrew and investigate the pathologic characteristics of induced breast precancerous lesions. The results indicated that 7,12-dimethylbenz(a)anthracene (DMBA) could induce breast lesions in tree shrews. However, comparing to DMBA alone, an addition of medroxyprogesterone acetate (MPA) to DMBA critically increased the rate of induced breast lesion in tree shrews. Half of induced breast lesions were intraductal papilloma and the others were atypical ductal hyperplasia. Induced lesions showed positive expression of estrogen receptor α (ERα), progesterone receptor (PR) and cytokeratin 5/6 (CK5/6), but negative expression of human epidermal growth factor receptor-2 (Her-2). The expression of B cell lymphoma-extra large (Bcl-xl) was significantly higher and the expression of B cell lymphoma 2 associated X protein (Bax) was significantly lower in the precancerous lesions (atypical ductal hyperplasia) compared to benign tumor (intraductal papilloma). These results suggest that DMBA is able to induce breast lesions in tree shrews. Combination of DMBA and MPA may be more effective to establish breast precancerous lesion tree shrew models. Tree shrew might be a promising animal model for studying the tumorogenesis of breast cancer.

Hepatitis A and Other Associated Hepatobiliary Diseases

“…Chile and Jordan have reported a decrease in anti-HAV sero-prevalence over the years [89,91]. The study conducted in Jordan showed a continual rise of the seroprevalence rates with rise in age.…”

“…The study conducted in Jordan showed a continual rise of the seroprevalence rates with rise in age. While, sero-prevalence was 26% among <2 years old, the rate increased to a whooping 94% for >20 years old [91]. A study conducted in Western Brazil revealed overall sero-prevalence among children as 16.7% in the year 2011, which significantly increased to 70.45% in a recently conducted survey [52,91].…”

Applications of Animal Models in Researching Hepatitis A

“…Chinese tree shrew (Tupaia belangeri chinensis), mainly distributing in Yunnan and Guangxi provinces in China, is a class of small animals having a closer evolutionary relationship with humans compared to rodents [91]. Tree shrews have emerged in the vision of scientists for more than 30 years as a result of having many valuable features that are suitable in animals utilized as experimental models in biomedical studies [92], particularly in the fields of toxicology and virology [93].…”

Characteristics of Angiotensin I-converting enzyme 2, type II transmembrane serine protease 2 and 4 in tree shrew indicate it as a potential animal model for SARS-CoV-2 infection

“…In recent years, several virus infection models, including influenza B [8], Zika virus [9], hepatitis C virus [10], and avian H5N1/ H9N2 influenza viruses [11,12], have been investigated by using tree shrews. Other human diseases, such as retinal vein pulsation and glaucoma of the visual system [13][14][15], myocardial ischemia and atherosclerosis of the cardiovascular system [16,17], nonalcoholic fatty liver [18], diabetic nephropathy [19] and obesity [20] of metabolism, cancers [21,22], Alzheimer's disease [23] and depression [24], all used tree shrews as disease models for their studies. However, the characteristics of ACE2, TMPRSS2 and TMPRSS4 in tree shrews have not been reported in most tissues or organs, and organs are more at risk for SARS-CoV-2 infection.…”