Application of transgenic mice to the molecular pathogenesis of cataract

One of the most prevalent disorders that cause blindness worldwide is cataract,and its essence is the visual disorder caused by the opacity of the lens.The significant degree of variation in cataracts and the fact that a variety of factors can impact a patient’s lens transparency make it especially crucial to investigate the pathogenesis of cataracts at the molecular level.It has been found that more than 60 genes are linked to the formation of cataracts,and the construction of a transgenic mouse model of cataract similar to the selection of human lens clouding due to a variety of causes has become an important means of studying the pathogenesis of cataract.Therefore,the research on the application of transgenic mice to the molecular pathogenesis of cataracts will be the main topic of this review of the literature.

Hepatitis B virus x gene and cyanobacterial toxins promote aflatoxin B_1-induced hepatotumorigenesis in mice

AIM： To assess the combinative role of aflatoxin B1 （AFB1）, cyanobacterial toxins （cyanotoxins）, and hepatitis B virus （HBV） x gene in hepatotumorigenicity. METHODS： One-week-old animals carrying HBV x gene and their wild-type littermates were intraperitoneally （ip） injected with either single-dose AFB1 [6 mg/kg body weight （bw）], repeated-dose cyanotoxins （microcystin- LR or nodularin, 10 μg/kg bw once a week for 15 wk）, DMSO （vehicle control） alone, or AFB1 followed by cyanotoxins a week later, and were sacrificed at 24 and 52 wk post-treatment. RESULTS： AFB1 induced liver tumors in 13 of 29 （44.8%） transcjenic mice at 52 wk post-treatment, significantly more frequent than in wild-type mice （13.3%）. This significant difference was not shown in the 24-wk study. Compared with AFB1 exposure alone, MC-LR and nodularin yielded approximately 3-fold and 6-fold increases in the incidence of AFB1-induced liver tumors in wild-type animals at 24 wk, respectively. HBV x gene did not further elevate the risk associated with coexposure to AFB1 and cyanotoxins. With the exception of an MC-LR-dosed wild-type mouse, no liver tumor was observed in mice treated with cyanotoxins alone at 24 wk. Neither DMSO-treated transgenic mice nor their wild-type littermates had pathologic alterations relevant to hepatotumorigenesis in even up to 52 wk. CONCLUSION： HBV x gene and nodularin promote the development of AFB1-induced liver tumors. Co-exposure to AFB1 and MC-LR tends to elevate the risk of liver tumors at 24 wk relative to exposure to one of them. The combinative effect of AFB1, cyanotoxins and HBVx on hepatotumorigenesis is weak at 24 wk.

Antiviral treatment of hepatitis B virus-transgenic mice by a marine organism, Styela plicata

AIM： To evaluate the antiviral effect of the effective ingredient of Styela plicata in a murine model of hepatitis B virus carrier. METHODS： HBV-transgenic mice were divided into 3 groups （control group, lamivudine treatment group and the effective ingredient of Styela plicata treatment group） and assigned to receive normal diet, lamivudine or the effective ingredient of Styela plicata for consecutive weeks. Serum hepatitis B surface antigen was detected by enzyme-linked immunosorbent assay （ELISA） method. Serum HBV DNA was detected by real-time polymerase chain reaction （RT-PCR）. Serum T helper （h） 1 cytokine interleukin （IL）-2 and Th2 cytokine IL-6 were detected by the quantitative sandwich enzyme immunoassay technique. Another group of HBV-transgenic mice was assigned to receive the effective ingredient of Styela plicata for consecutive weeks. The histology of liver tissue was evaluated before and after treatment. RESULTS： Twelve weeks after starting the therapy, serum hepatitis B surface antigen was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet （F12wk = 88.81, P12wk = 0.000 〈 0.01）. Serum HBV DNA was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet （F12wk = 20.71, P12wk = 0.000 〈 0.01）. However, like lamivudine, the effective ingredient of Styela plicata could not inhibit the replication of HBV completely. A rebound phenomenon of hepatitis B surface antigen and HBV DNA in sera could be found 4 wk after withdrawal of medication. Eight weeks after starting the therapy, serum levels before and after Styela plicata treatment of IL-2 were 2.41 ± 0.38 and 10.56 ± 0.78 ng/L, respectively （t8wk = -16.51, P8wk = 0.000 〈 0.01）. Compared with the serum levels of IL-2 in the normal diet-treated mice （2.48 ± 0.17 ng/L; t8wk = 13.23, P8wk = 0.000 〈 0.01）. Serum levels before and after Styela plicata treatment of IL-6 were 63.62 ± 6.31 and 54.52 ± 6.22 ng/L, respectively, compared with the serum levels of IL-6 in the normal diet-treated mice （60.84 ± 4.21 ng/L）. Histological analysis of liver from Styela plicata-treated HBV-transgenic mice also showed catabatic status in inflammation and hepatitis B surface antigen. CONCLUSION： Styela plicata may be an effective anviral medicine in treating chronic hepatitis B.

Overexpression of γ-aminobutyric acid transporter subtype I leads to susceptibility to Kainic acid-induced seizure in transgenic mice

γ-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter, and the GABAergic synaptic transmission is normally terminated by the rapid uptake through GABA transporters. With transgenic mice ubiquitously overexpressing GABA transporter subtype I (GAT1), the present study explored the pathophysiological role of GAT1 in epileptogenesis. Though displaying no spontaneous seizure activity, these mice exhibit altered electroencephalographic patterns and increased susceptibility to seizure induced by kainic acid. In addition, the GABAA receptor and glutamate transporters are up-regulated in transgenic mice, which perhaps reflects a compensatory or corrective change to the elevated level of GAT1. These preliminary findings support the hypothesis that excitatory and inhibitory neurotransmission, and seizure susceptibility can be altered by neurotransmitter transporters.

Generation of the regulatory protein rtTA transgenic mice

AIM: To translate Tet-on system into a conditional mouse model, in which hepatitis B or C virus (HBV or HCV) gene could be spatiotemporally expressed to overcome 'immune tolerance' formed during the embryonic development and 'immune escape' against hepatitis virus antigen(s), an effector mouse, carrying the reverse tetracycline-responsive transcriptional activator (rtTA) gene under the tight control of liver-specific human apoE promoter, is required to be generated. METHODS: To address this end, rtTA fragment amplified by PCR was effectively inserted into the vector of pLiv.7 containing apoE promoter to create the rtTA expressing vector, I.e., pApoE-rtTA. ApoE-rtTA transgenic fragment (-6.9 kb) released from pApoE-rtTA was transferred into mice by pronucleus injection, followed by obtaining one transgene (+) founder animal from microinjection through PCR and Southern blot analysis.RESULTS: rtTA transgene which could be transmitted to subsequent generation (F1) derived from founder was expressed in a liver-specific fashion. CONCLUSION: Taken together, these findings demonstrate that rtTA transgenic mice, in which rtTA expression is appropriately targeted to the murine liver, are successfully produced, which lays a solid foundation to 'off-on-off' regulate expression of target gene (s) (e.g., HBV and/or HCV) in transgenic mice mediated by Tet-on system.

Tetrahydroxy Stilbene Glucoside Ameliorates Cognitive Impairments and Pathology in APP/PS1 Transgenic Mice

Cognitive impairment is the main clinical manifestation of Alzheimer's disease(AD),and amyloid-β(AB)deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains.This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside(TSG)on cognitive function in APP/PS 1 mice during long-term administration.Here,we treated APP/PS1 model mice of AD with different doses of TSG(50 mg/kg and 100 mg/kg)for 5 to 17 months by gavage,and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests,and investigated the possible mechanisms by immunohistochemistry and Western blotting.Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test.Furthermore,Aβ40/42 deposition in the cortex and hippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique.Finally,Western blotting showed that TSG primarily decreased the APP expression to avoid the Aβplaque deposition in the cortex and hippocampus of mice.These results reveal the beneficial effects of TSG in APP/PSI-AD mice,which may be associated with the reduction of Aβdeposits in the brain.

Overexpression of NK2 inhibits liver regeneration after partial hepatectomy in mice

AIM： To investigate the in vivo effects of NK2 on liver regeneration after partial hepatectomy （PH）. METHODS： Survival after PH was observed with 21 NK2 transgenic mice and 23 wild-type （WT） mice over 10 d. Liver regeneration was analyzed using histology and immunohistochemistry. Expressions of genes were analyzed using Northern blot analysis, immunoprecipitation and immunoblotting, and reverse transcriptase polymerase chain reaction assay. Kaplan Meier method and the log-rank test were used for analyzing the survival after PH. Differences in the results of immunohistochemistry and percentage of liver regeneration was determined by the Student＇s t-test. RESULTS： More than half of NK2 transgenic mice died within 48 h after PH. After PH, increased deposition of small lipid droplets in hepatocytes was evident and hepatic proliferation was inhibited in NK2 transgenic mice. The hepatic expression and kinase activity of HGF receptor, c-Met, were unchanged among WT mice and NK2 transgenic mice after PH. The expression of tumor necrosis factor-co （TNF-c0 and interleukin-6 （IL-6） in liver tissues were prolonged in NK2 transgenic mice that died after PH. CONCLUSION： Our findings indicate that overexpression of NK2 inhibits liver regeneration after PH.

Increased susceptibility to experimental steatohepatitis induced by methionine-choline deficiency in HBs-Tg mice

BACKGROUND: Worldwide, about 25% of individuals with chronic hepatitis B have fatty liver disease. Lipogenic diets that are completely devoid of methionine and choline induce nonalcoholic fatty liver disease. However, no animal model of nonalcoholic steatohepatitis associated with HBV infection is available, and the influence of viral infection on nutritional hepatic steatosis is unclear. METHODS: We used HBV surface antigen transgenic mice (HBs-Tg mice), which mimic healthy human carriers with hepatitis B surface antigen. The mice were fed with a high-fat methionine-choline-deficient diet (MCD) to build a reliable rodent nutritional model of nonalcoholic steatohepatitis associated with HBV infection, and the changes in body weight and serum triglycerides were measured. Hepatocyte ballooning changes were determined by hematoxylin and eosin staining. The extent of hepatic fat accumulation was evaluated by oil red O staining. Immunohistochemical assays were performed to detect proliferating cell nuclear antigen as an index of cell proliferation. RESULTS: MCD feeding provoked systemic weight loss and liver injury. MCD feeding caused more macrovesicular fat droplets and fat accumulation in the livers of HBs-Tg mice than in wild-type C57BL/6 mice. In addition, within 30 days of MCD exposure, more PCNA-positive nuclei were found in the livers of HBs-Tg mice. CONCLUSIONS: HBs-Tg mice fed with a lipogenic MCD form more macrovesicular fat droplets earlier, coincident with more hepatocyte proliferation, resulting in the appearance of increased susceptibility to experimental steatohepatitis in these mice.

Rescue of the albino phenotype by introducing a functional tyrosinase minigene into Kunming albino mice

AIM： To use the tyrosinase minigene as a visual marker to perform microinjection training and improve the techniques related with transgene to greatly elevate the effidency of gene transfer. METHODS： A mouse tyrosinase minigene, i.e., TyBS, in which the 2.25-kb authentic genomic 5＇ non-coding flanking sequence of mouse tyrosinase was fused to a mouse tyrosinase cDNA, was introduced into the fertilized eggs of outbred Kunming albino mice. RESULTS： Of the 11 animals that developed from the injected eggs, two mice （P1 and #8） exhibited pigmented hair （P1） and eyes （P1 and #8）, as confirmed by PCR analysis for the tyrosinase minigene integrated into the genome. When founder P1 was bred to Kunming male mouse, six progeny out of 11 offspring inherited the transgene and the pigmented-eye phenotype. CONCLUSION： Taken together, these results suggest that this minigene encodes the active tyrosinase protein and that its 5＇ flanking region contains the sequences regulating the expression of mouse tyrosinase gene as expected. We have rescued the albino phenotype by introduction and expression of a functional tyrosinase minigene in the Kunming albino mouse and the transgene can be passed to subsequent generation. These findings also indicate that TyBS can be a useful visual marker gene in the co-transgenic experiments.

Establishment of Hamster-and Human-PRNP Transgenic Mice

Objective To create transgenic mice expressing hamster- and human-PRNP as a model tor understanding the physiological function and pathology of prion protein （PrP）, as well as the mechanism of cross-species transmission of transmissible spongiform encephalopathies （TSEs）. Methods Hamster and human-PRNP transgenic mice were established by conventional methods. The copy number of integrated PRNP in various mouse lines was mapped by real-time PCR. PRNP mRNA and protein levels were determined by semi-quantitative RT-PCR, real-time RT-PCR, and western blot analysis. Histological analyses of transgenic mice were performed by hematoxylin and eosin （H ＆ E） staining and immunohistochemical （IHC） methods. Results Integrated PRNP copy number in various mouse lines was 53 （Tg-haPrP1）, 18 （Tg-huPrP1）, 3 （Tg-huPrP2）, and 16 （Tg-huPrP5）, respectively. Exogenous PrPs were expressed at both the transcriptional and translational level. Histological assays did not detect any abnormalities in brain or other organs. Conclusion We have established one hamster-PRNP transgenic mouse line and three human-PRNP transgenic mouse lines. These four transgenic mouse lines provide ideal models for additional research.

Carboxymethytl Pachymaram Up-Regulates Dendritic Cell's Function in Hepatitis B Virus Transgenic Mice in vitro

The effect ofcarboxymethytl pachymaram （ CMP ） on the function of dendritic cells（DCs） derived from spleens of hepatitis B virus transgenic mice are studied in vitro. The phenotypes of DCs are tested by flow cytometry （FCM）, cytokines measured by ELISA. The expression of DCs＇ phenotypes in IdBV transgenic mice are low （CD80^＋CD11c^＋：59.12±11.53 vs 9,60±4.53, p〈0.01; CD80^＋ MHC-Ⅱ^＋： 44.86±12.31 vs 9.80±5,72, p〈0.01, normal mice vs HBV transgenic mice）, the ability of DCs stimulating T lymphocytes proliferation decreases （0.37±0.11 vs 0.20±0,11, p〈0.05, normal mice vs HBV transgenic mice）, levels of IL-12 and IFN-y decrease whereas the level of IL-10 increases; CMP can enhance DCs＇ ability of stimulating T lymphocytes proliferation, facilitate the secretion of IL-12 and IFNp, inhibit the secretion of IL-10, thus up regulates DCs function. The results show a good prospective use of CMP on the treatment of chronic hepatitis B.

Protective Effects of Overexpression of bcl-xl Gene on Local Cerebral Infarction in Transgenic Mice Undergoing Permanent Occlusion of Middle Cerebral Artery

In order to investigate the protective effects of the overexpression of bcl-xl gene on local cerebral infarction in the transgenic mice subject to permanent occlusion of middle cerebral artery, the models of bcl-xl transgenic mice were established and subjected to cerebral infarction by intraluminal occlusion of the middle cerebral artery. The infarct volume and the neurological scores were observed and comparison between the wild type mice and the transgenic mice was made. It was found that the infarct volume and the neurological scores in the transgenic mice were significantly decreased as compared with those in the wild type mice. It was suggested that the overexpression of bcl-xl gene in transgenic mice could reduce the infarct volume and improve the neurological function of the mice.

Muscle hypertrophy in transgenic mice due to over-expression of porcine myostatin mutated at its cleavage site

Myostatin, a member of the transforming growth factor beta（TGF-β） superfamily, is a dominant inhibitor that acts to limit skeletal muscle growth and development. In this study, we generated transgenic mice that express porcine myostatin containg mutations at its cleavage site（RSRR） to evaluate its effect on muscle mass. Results showed that the weight of four skeletal muscles including gastrocnemius, rectus femoris, tibialis anterior, and pectoralis increased by 17.83 and 28.39%, 21.76 and 28.70%, 34.31 and 41.62%, 53.21 and 27.54% in transgenic male and female mice, respectively, compared to their corresponding non-transgenic control mice. Measurement of muscle fiber size and number indicated that the mean myofiber size increased by 50.73 and 61.30% in transgenic male and female mice respectively compared to the non-transgenic controls. However, there was no difference in the number of myofiber between transgenic and non-transgenic male mice. These results clearly demonstrated that the increase in skeletal muscle mass in transgenic mice is caused by hypertrophy instead of hyperplasia.

Antiviral effect of Chinese medicine jiaweisinisan in hepatitis B virus transgenic mice

AIM： To study the antiviral effect of Chinese medicine jiaweisinisan （JWSNS） on hepatitis B virus （HBV） infection in transgenic mice （TGM）. METHODS： Twenty two 6-8 wk old HBV TGM in the third generation were divided into TGM control group and TGM treated group randomly. The normal control group included ten normal BC 57L/6 mice at the same age. The mice in treated group were administrated with JWSNS at the concentration of 4 g/mL and the dosage of 50 g/kg per d for 30 d, while the mice in TGM control group and normal control group were administrated with normal saline at the same dosage and the same time. Polymerase chain reaction （PCR） was used to assess the contents of HBV DNA in serum of HBV TGM before and after treatments, whereas blot hybridization was utilized to measure the contents of HBV DNA in the liver of both HBV TGM and normal BC 57L/6 mice. RESULTS： The levels of serum HBV DNA in TGM treated group were remarkably decreased after the treatment of JWSNS （7.662±0.78 vs 5.22±3.14, P〈0.05）, while there was no obvious change after administration of normal saline in TGM control group （7.125±4.26 vs 8.932 ± 5.12, P〉 0.05）. The OD values of HBV DNA in the livers of the mice in TGM treated group were significantly lower than those of TGM control group （0.274±0.096 vs 0.432 ± 0.119, P 〈 0.01）. CONCLUSION： JWSNS exerts suppressive effects on HBV DNA in the serum and liver of TGM.

Inducible overexpression of porcine homeobox A10 in the endometrium of transgenic mice

Homeobox A10 （HOXA 10） is a well-known transcription factor that plays an important role in directing endometrial differ- entiation and establishing the conditions required for implantation. Interestingly, the expression level of HOXAIO may be associated with litter size. To study the effects of the porcine HOXAIO promoter fragment on the expression of HOXAIO gene in vivo, we generated a transgenic mouse model using pronuclear microinjection, and measured the expression of HOXAIO in the endometrium. There was no difference in the expression level of HOXAIO between transgenic and wild- type mice in the absence of hormone stimulation. However, following treatment with progesterone and estradiol benzoate, the expression level of HOXAIO was significantly increased in transgenic mice compared with that of wild-type mice. Fur- thermore, the litter size of transgenic females was larger than that of wild-type females （7.02±1.73 vs. 6.48＋1.85; P=0.14）. Moreover, the difference of litter size was greater in the later parities （7.33±1.62 vs. 6.37±2.02; P=0.08） compared with the first parity （6.76±1.81 vs. 6.61v1.67; P=0.77） between transgenic and wild-type mice. Therefore, our transgenic mouse model provides exciting insights regarding the actions of HOXAIO and its hormone-inducible promoter in vivo. The present study offers valuable proof of principle to develop transgenic pigs with a hormone-inducible promoter regulating HOXAIO to alter litter size.

Protective effects on acute hypoxic-ischemic brain damage in mfat-1 transgenic mice by alleviating neuroinflammation

Acute hypoxic-ischemic brain damage(HIBD)mainly occurs in adults as a result of perioperative cardiac arrest and asphyxia.The benefits of n-3 polyunsaturated fatty acids(n-3 PUFAs)in maintaining brain growth and development are well documented.However,possible protective targets and underlying mechanisms of mfat-1 mice on HIBD require further investigation.The mfat-1 transgenic mice exhibited protective effects on HIBD,as indicated by reduced infarct range and improved neurobehavioral defects.RNA-seq analysis showed that multiple pathways and targets were involved in this process,with the anti-inflammatory pathway as the most significant.This study has shown for the first time that mfat-1 has protective effects on HIBD in mice.Activation of a G protein-coupled receptor 120(GPR120)-related anti-inflammatory pathway may be associated with perioperative and postoperative complications,thus innovating clinical intervention strategy may potentially benefit patients with HIBD.

The Establishment of Double-Transgenic Mice that Co-Express the appA and MxA Genes Mediated by Type A Spermatogonia In vivo

Type A spermatogonial stem cells are the only immortal diploid cells in the postnatal animal that undergo self-renewal through the lifetime of an animal and transmit genes to subsequent generations. In this paper, the generation and characterization of double-transgenic mice co-expressing the Escherichia coli appA gene and human MxA gene generated via the in vivo transfection of type A spermatogonial cells were reported for the ifrst time. The dicistronic expression vector pcDNA-appA-MxA（AMP） and ExGen500 transfection reagent were injected into the testicular tissue of 7-d-old male ICR mice. The mice that underwent testis-mediated gene transfer were mated with wild-type female mice, and the integration and expression of the foreign genes in the offspring were evaluated. Transgenic mice that co-expressed appA and MxA showed a gene integration rate of 8.89%（16/180）. The transgenic mice were environmentally friendly, as the amount of phosphorous remaining in the manure was reduced by as much as 11.1%by the appA gene （P〈0.05）;these animals also exhibited a strong anti-viral phenotype.

Effect of Yangqixue Qufengshi Recipe (养气血祛风湿方) on Rheumatoid Arthritis Model Mice under Different Genetic Backgrounds

Objective： To study the effect of Yangqixue Qufengshi Recipe （养气血祛风湿方, YQXQFS） on rheumatoid arthritis （RA） model mice under different genetic backgrounds. Methods： Collagen Induced Arthritis （CIA） were established on HLA-DR4 transgenic （TG） mice and non-transgenic （NTG） mice, which partly were raised with YQXQFS, and the onset day of CIA, the level of type Ⅱ collagen （C Ⅱ ）-reactive antibodies and the pathological scores of CIA were assessed. Results： Under HLA-DR4 TG background （compared with NTG mice）, the earlier onset day of CIA （ 11.22±3.35 days vs 16.56 ±4.75 days, P〈0.05） and higher level of C Ⅱ-reactive antibodies （0. 2274±0. 1390μg/ml vs 0.1101±0. 0560μg/ml, P〈0.05） were observed, but the pathological scores of CIA remained unchange. YQXQFS could not influence the onset day of CIA and the level of C Ⅱ-reactive antibodies, but had a certain effect on the total pathological scores （6.56±3.43 scores vs 11.11±5.64 scores） and bone erosion （0.22±0.44 scores vs 1.67±1.50 scores） of CIA on NTG mice （P〈0.05）, NTG YQXQFS group compared with NTG experimental group. Conclusion： YQXQFS had a certain effect on RA model, but had no significant effect on HLA-DR4 related CIA.

Age-related Changes in Familial Hypertrophic Cardiomyopathy Phenotype in Transgenic Mice and Humans

β-myosin heavy chain mutations are the most frequently identified basis for hypertrophic cardiomyopathy （HCM）. A transgenic mouse model （αMHC403） has been extensively used to study various mechanistic aspects of HCM. There is general skepticism whether mouse and human disease features are similar. Herein we compare morphologie and functional characteristics, and disease evolu- tion, in a transgenic mouse and a single family with a MHC mutation. Ten male αWHC403 transgenic mice （at -5 weeks, -12 weeks, and -24 weeks） and 10 HCM patients from the same family with a β-myosin heavy chain mutation were enrolled. Morphometric, conventional echocardiographic, tissue Doppler and strain analytic characteristics of transgenic mice and HCM patients were assessed. Ten male transgenic mice （αMHC403） were examined at ages -5 weeks, -12 weeks, and -24 Weeks. In the transgenic mice, aging was associated with a significant increase in septal （0.59±0.06 vs. 0.64±-0.05 vs. 0.69±0.11 mm, P〈0.01） and anterior wall thickness （0.58±0.1 vs. 0.62±0.07 vs. 0.80-1-0.16 mm, P〈0.001）, which was coincident with a significant decrease in circumferential strain （-22%=1=4% vs. -20%-4-3% vs. -19%-4-3%, P=0.03）, global longitudinal strain （-19%-4-3% vs. -17%-4-2% vs. -16%±3%, P=0.001） and E/A ratio （1.9±0.3 vs. 1.7-4-0.3 vs. 1.4-4-0.3, P=0.01）. The HCM patients were classified into 1st generation （n=6; mean age 534-6 years）, and 2nd generation （n=4; mean age 32＋8 years）. Septal thickness （2.2±0.9 vs. 1.4±0.1 cm, P〈0.05）, left atrial （LA） volume （62±16 vs. 41±5 mL, P=0.03）, E/A ratio （0.77±0.21 vs. 1.1±0.1, P=0.01）, E/e＇ ratio （25±10 vs. 12±2, P=0.03）, global left ventricular （LV） strain （-14%±3% vs. -20%±3%, P=0.01） and global LV early diastolic strain rate （0.76±0.17 s1 vs. 1.3±0.2 s-1, P=0.01） were significantly worse in the older generation. In β-myosin heavy chain muta- tions, transgenic mice and humans have similar progression in morphologic and functional abnormali- ties. The αMHC4±3 transgenic mouse model closely recapitulates human disease.

Study on Expression of KLF4 in Her2 Over-expressed Transgenic Mice

[Objective]The aim was to study the biological characteristics of Her2 over-expressed transgenic mice and to detect the changes in expression of KLF4. [Method] On the basis of establishment of Her2 over-expressed transgenic mice, the population was expanded by propagation. The genotype of the offspring was identified by PCR, the body weight-age curve was drawn, and the expression of KLF4 （FL） and KLF4α was detected by RT-PCR. [Result] In the Her2-overex-pressed breast cancer-positive mice, the expression level of KLF4α decreased slightly in the course of breast cancer, and the expression level of KLF4 （FL） was increased significantly compared with those in normal mice. However, the expression level of KLF4 gene in the breast cancer-positive mice showed a downward trend. [Conclusion] This study will fill the gaps in the study of KLF4 at the animal model level and complete the study on relationship between KLF4 and the occurrence and development of breast cancer.