• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.161-161
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• 2003

Different circling preference of mice is a reference of inter-individual differences in their endogenous neuroimmune circuits. I have investigated relationship between differential immune responses in mice, who have same age, gender, and genetic background, and circling behavior preference.(omitted)

• Reproductive and Developmental Biology
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• v.34 no.2
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• pp.63-71
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• 2010

The spontaneous mutant circling mouse (cir/cir) shows a circling behavior and hearing loss. We produced transgenic mice overexpressing transmembrane inner ear (tmie) gene, the causative gene, for the phenotypic rescue of the circling mouse. Through the continuous breeding with circling mice, the cir/cir homozygous mice carrying the transgene (cir/cir-tg) were produced. The rescued cir/cir-tg mice were able to swim in the water with proper orientation and did not show any circling behavior like wild type mice. Western blot and immunohistochemical analysis exhibited that the transgenic tmie was expressed in the inner ear. Inner and outer hair cells were recovered in the cochlea and spiral ganglion neurons were also recovered in the rescued mice. Auditory brainstem response (ABR) test demonstrated that the cir/cir-tg mice are able to respond to sound. This study demonstrates that tmie transgene can recover the hearing impairment and abnormal behavior in the circling mouse.

• Proceedings of the KSAR Conference
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• 2004.06a
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• pp.226-226
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• 2004

Circling (cir) mouse is a spontaneous mutant in the inner ear that was first reported in Korea. The mutation is transmitted by an autosomal recessive gene with 100 %- penetrance.. Homozygous mice are characterized by head-tossing, bi-directional circling behavior and deafness. Histologicalexamination of the inner ear reveals abnormalities of the region around the organ of Corti, spiral ganglion neurons, and outer hair cells. (omitted)

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.161-161
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• 2003

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.383-388
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• 2015

$K^+$ outward currents in the outer hair cells (OHCs) of circling mice (homozygous (cir/cir) mice), an animal model for human deafness (DFNB6 type), were investigated using a whole cell patch clamp technique. Littermate heterozygous (+/cir) mice of the same age (postnatal day (P) 0-P6) were used as controls. Similar slow rising $K^+$ currents were observed in both genotypes, but their biophysical and pharmacological properties were quite different. The values of Vhalf for activation were significantly different in the heterozygous (+/cir) and homozygous (cir/cir) mice ($-8.1{\pm}2.2mV$, heterozygous (+/cir) mice (n=7) and $-17.2{\pm}4.2mV$, homozygous (cir/cir) mice (n=5)). The inactivation curve was expressed by a single first order Boltzmann equation in the homozygous (cir/cir) mice, while it was expressed by a sum of two first order Boltzmann equations in the heterozygous (+/cir) mice. The $K^+$ current of homozygous (cir/cir) mice was more sensitive to TEA in the 1 to 10 mM range, while the 4-AP sensitivities were not different between the two genotypes. Removal of external $Ca^{2+}$ did not affect the $K^+$ currents in either genotype, indicating that the higher sensitivity of $K^+$ current to TEA in the homozygous (cir/cir) mice was not due to an early expression of $Ca^{2+}$ activated $K^+$ channels. Our results suggest that the $K^+$ outward current of developing homozygous (cir/cir) mice OHCs is different in both biophysical and pharmacological aspects than that of heterozygous (+/cir) mice.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.251-257
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• 2017

Inhibition of $K^+$ outward currents by linopirdine in the outer hair cells (OHCs) of circling mice (homozygous (cir/cir) mice), an animal model for human deafness (DFNB6 type), was investigated using a whole cell patch clamp technique. Littermate heterozygous (+/cir) and ICR mice of the same age (postnatal day (P) 0 -P6) were used as controls. Voltage steps from -100 mV to 40 mV elicited small inward currents (-100 mV~-70 mV) and slow rising $K^+$ outward currents (-60 mV~40 mV) which activated near -50 mV in all OHCs tested. Linopirdine, a known blocker of $K^+$ currents activated at negative potentials ($I_{K,n}$), did cause inhibition at varying degree (severe, moderate, mild) in $K^+$ outward currents of heterozygous (+/cir) or homozygous (cir/cir) mice OHCs in the concentration range between 1 and $100{\mu}m$, while it was apparent only in one ICR mice OHC out of nine OHCs at $100{\mu}m$. Although the half inhibition concentrations in heterozygous (+/cir) or homozygous (cir/cir) mice OHCs were close to those reported in $I_{K,n}$, biophysical and pharmacological properties of $K^+$ outward currents, such as the activation close to -50 mV, small inward currents evoked by hyperpolarizing steps and TEA sensitivity, were not in line with $I_{K,n}$ reported in other tissues. Our results show that the delayed rectifier type $K^+$ outward currents, which are not similar to $I_{K,n}$ with respect to biophysical and pharmacological properties, are inhibited by linopirdine in the developing (P0~P6) homozygous (cir/cir) or heterozygous (+/cir) mice OHCs.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.90-90
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• 2003

Circling mice were recorded to display profound deafness and a head-tossing and bidirectional circling behavior, showing an autosomal recessive mode of inheritance. In addition, the histological examination of inner ears revealed that the region around organ of Corti, spiral ganglion neurons and outer hair cells showed definite abnormality. On the other hand, a genetic linkage map was constructed in an intraspecific backcross between cir and C57BL/6J mice. The cir gene was mapped to a region between D9Mitl16/D9Mit15 and D9Mit38 on the mouse chromosome 9. Estimated distances between cir and D9Mitl16, and between cir and D9Mit38 are 0.70 $\pm$ 0.40 and 0.23 $\pm$ 0.23 cM, respectively. The markers in order was defined as follows: centromere-D9Mit182- D9Mit51/ D9Mit79/ D9Mit310- D9Mit212/ D9Mit184- D9Mit116/ D9Mit15- cir- D9Mit38- D9Mit20- D9Mit243- D9Mit16- D9Mit55/ D9Mit125- D9Mit281 Based on genetic mapping, we constructed for a YAC contig across cir region. They covered the entire region or cir and cir gene was located on between the lactotransferrin (ltf) and the macrotubule-associated protein (map4). It is known that sr gene is localized in 64cM of mouse chromosome 9. The two mouse were found to be allelic by complementation test. Recently the spinner mouse has been mapped to our cir region, and tmie gene were elucidated. And further study will be needed in circling mouse to prove tmie gene mutaiton.

• Toxicological Research
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• v.24 no.1
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• pp.59-68
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• 2008

N-ethyl-N-nitrosoures (ENU) is effective in inducing hypermorphic mutation as well as hypomorphic and antimorphic mutations. Therefore, this mutagen is used to the production of mutant in the mice. In order to perform an effective ENU mutagenesis using BALB/cAnN mice, determination of optimal dosage and dosage regimen of ENU is necessary. And this study tried to develop a suitable screening method and searched for novel and various mutants as model animals in phenotypedriven ENU mutagenesis. We have carried out dosage regimen for mutagenizing dose of 200 mg/kg ENU in the BALB/c mice. Total screened mice were 30,133. As the results of Esaki and Cho's Phenotype Screening, we got 2,516 phenotypic and behavior abnormalities in $G_1,\;G_2\;and\;G_3$ mice. One hundred thirty five $G_1$ phenodeviants were tested for inheritance and 16 dominant mutants were discovered. Forty two recessive mutants were also found in tested 201 micropedigrees. Early-onset mutant mice included the dysmorphology of face, eye, tail, limb, skin, and foot and abnormal behavior like circling, swimming, head tossing, stiff-walking, high cholesterol level, and tremor etc. In this study we could effectively screen $G_3$ recessive mutants. The frequent and concise early-onset screening before weaning will be available for ENU mutagenesis.

• Proceedings of the KSAR Conference
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• 2001.03a
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• pp.48-48
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• 2001

A new neurological mutant has been found in the ICR outbred strain mouse. Affected mice display profound deafness and a head-tossing and bidirectional circling behavior, showing an autosomal recessive mode of inheritance. It was, therefore, named cir/Kr with the gene symbol cir. The auditory tests identified clearly the hearing loss of the cir mice when compared to wild type mice. Pathological studies confirmed the developmental defects in the middle ear, cochlea, cochlear nerve, and semicircular canal areas, which were correlated to the abnormal behavior observed in the cir mice. Thus, cir mice may be useful as a model for studying inner ear abnormalities and deafness. We have constructed a genetic linkage map by positioning 14 microsatellite markers across the (cir) region and intraspecific backcross between cir and C57BL/6J mice. The cir mouse harbors an autosomal recessive mutation on mouse chromosome 9. The cir gene was mapped to a region between D9Mit116 and D9Mit38 Estimated distances between cir and D9Mit116, and between cir and D9Mit38 are 0.7 and 0.2 cM, respectively. The gene in order was defines : centromere-D9Mit182-D9Mit51/D9Mit79/D9Mit310-D9Mit212/D9Mit184-D9Mit116-cir-D9Mit38-D9Mit20-D9Mit243-D9Mit16-D9Mit55/D9Mit125-D9Mit281. The mouse map location of the cir locus appears to be in a region homologous to human 3q21. Our present date suggest that the nearest flanking marker D9Mit38 provides a useful anchor for the isolation of the cir gene in a yeast artificial chromosome contig.

• Korean Journal of Veterinary Service
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• v.17 no.1
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• pp.67-80
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• 1994

8-10 week old ICR mice were infected intracerebrally and intraperitoneally with different encephalomyocarditis virus(K$_3$, $K_{11}$, ATT-VR 129) to observe histopathological and immunohistochemical change. Results obtained throuh the experiments were summarized as follows : 1. No differences in clinical signs by the virus strains and the inoculation routes were found. Mice infected with EMCV showed clinical signs after 3 days of inoculation. Main clinical signs were tremors, convulsions, circling movement, and uni or bilateral hindleg paralysis followed by death on the 3-8 days. In general, most of the infected animals died or recovered closely on the 8th day of postinoculation. 2. At necropsy, petechial and ecchymotic hemorrhages in lung were observed and no specific findings in other were observed. 3. In histopathological observation, neuroal cell degeneration perivascular mononucear cell in-filtration gliosis were appeared in central nervous system. Myocarditis with myocardial degeneration and necrosis, calcification were observed along with acinar cell necrosis of exocrine glands in pancreas, severe glomerulonephritis in kidney. Also, focal necrosis of hepatocytes and interstitial pneymonia hyperemia, hemorrhages in lungs were observed. 4. By immunohistochemical staining using ABCIT method, the positive cells were recognized in intracytoplasm of acinar cell in pancreas and intracytoplasm of neuronal cells in cerebrum.