麋鹿鹿角生长周期及影响因子

2013年8月至2014年8月,使用望远镜(SWAROVSKI 8×42 WB)和照相机(Canon 550D 70×300)观察北京南海子59只雄性麋鹿茸的生长和角脱落周期,发现麋鹿角总体趋势呈随着年龄的减少,脱角日期越迟,且等级序位高或者鹿王较年老个体先脱落。收集2012年12月至2014年2月两年度麋鹿自然脱落的角,研究表明,个体而言,左右角脱角顺序差异明显,同一天脱落两角者占17.0%,左角先脱落者占34.1%,右角先脱落者占48.8%,重量重和重量轻的角先脱落的个体各占41.5%,个体成对的左右角脱落时间间隔短,平均为1.98d;群体而言,角重量与脱角时间呈显著负相关,总体呈现角重的个体角先脱落,但不是角最重的个体角第一个脱落。2013年6月至2014年5月,对北京南海子、湖北石首、江苏大丰、天津七里海、浙江慈溪、浙江临安、海南海口、河北滦河上游、辽阳千山等9个地区麋鹿种群麋鹿角脱落起止时间进行调查,研究表明野生种群脱角时间比圈养种群早;迁入热带地区海南的麋鹿仍有规律的角周期;同一栖息地不同年份角周期存在差异,不同栖息地间麋鹿角周期存在差异;脱角起始时间与海拔、经度、纬度、年平均气温、圈养情况和气候类型等影响因子不存在统计学上显著的相关性,但光周期和激素直接主导和调节着角周期,年龄大小、角重量、营养以及与营养相关的能量、种群密度、物候等环境因子均影响角周期。     

The effect of anti-adhesion molecule antibody on the development of collagen-induced arthritis.

In order to study how inflammatory cells including autoimmune lymphocytes interact with each other to develop collagen-induced arthritis (CIA), we injected monoclonal antibodies against mouse LFA-1 and ICAM-1 into DBA/1 mice immunized with type II collagen (CII). Both antibodies suppressed the development of CIA. These antibodies showed no effect on anti-CII antibody response, although they both significantly suppressed DTH response. It was suggested that anti-adhesion molecule antibodies suppress CIA mainly through their effect on cell-mediated immunity, without affecting humoral immunity under the conditions used.     

Enhancement of exercise endurance capacity by fermented deer antler in BALB/c mice

To investigate the activity of fermented deer antler on exercise endurance capacity, we evaluated endurance capacity in five-week-old male BALB/c mice by administering the fermented deer antler extract (FA) or the non-fermented deer antler extract (NFA) and then subjected the mice to exercise in the form of swimming. The mice administered 500?mg/kg/day of FA showed a significant increase in swimming time compared with mice administered placebo (16.55?min vs. 21.64?min, P?<?0.05). Serum lactate dehydrogenase (LDH), the marker of the liver and muscle damage, was significantly lower in FA groups. However, NFA groups did not show significantly different swimming time or serum LDH from that of the control group. Moreover, the FA-500 group had significantly higher hepatic superoxide dismutase (SOD) activity after forced swimming than the control and NFA groups (P?<?0.05). These findings suggest that fermentation may increase the exercise endurance capacity of the deer antler.     

White-Tailed Deer Antler Research: A Critique of Design and Analysis Methodology

ABSTRACT Debate within the popular and technical literature regarding predictability of antler size at maturity based on 1.5-year antler size in white-tailed deer (Odocoileus virginianus) has led to confusion and uncertainty within constituent groups. Koerth and Kroll (2008) provided measures of age-related antler development using recaptures of known-age males from 12 deer populations in southern Texas. Several design and analysis issues reduce the scope and validity of their conclusion that amount of growth in the first set of antlers was a poor predictor of antler growth at maturity. Although unstated, the statistical hypothesis they tested did not coincide with their specific conclusions. Using a simulation, we show that their methods were susceptible to measurement bias. Their results are applicable only to populations with similar culling and management programs. Additionally, we provide recommendations for future research projects that evaluate predictability of antler size at maturity based on antler size at younger ages.     

Hydroxyl radical modification of collagen type II increases its arthritogenicity and immunogenicity

Background

The oxidation of proteins by endogenously generated free radicals causes structural modifications in the molecules that lead to generation of neo-antigenic epitopes that have implications in various autoimmune disorders, including rheumatoid arthritis (RA). Collagen induced arthritis (CIA) in rodents (rats and mice) is an accepted experimental model for RA.

Methodology/Principal Findings

Hydroxyl radicals were generated by the Fenton reaction. Collagen type II (CII) was modified by ^•OH radical (CII-OH) and analysed by ultraviolet-visible (UV-VIS), fluorescence and circular dichroism (CD) spectroscopy. The immunogenicity of native and modified CII was checked in female Lewis rats and specificity of the induced antibodies was ascertained by enzyme linked immunosorbent assay (ELISA). The extent of CIA was evaluated by visual inspection. We also estimated the oxidative and inflammatory markers in the sera of immunized rats. A slight change in the triple helical structure of CII as well as fragmentation was observed after hydroxyl radical modification. The modified CII was found to be highly arthritogenic and immunogenic as compared to the native form. The CII-OH immunized rats exhibited increased oxidative stress and inflammation as compared to the CII immunized rats in the control group.

Conclusions/Significance

Neo-antigenic epitopes were generated on ^•OH modified CII which rendered it highly immunogenic and arthritogenic as compared to the unmodified form. Since the rodent CIA model shares many features with human RA, these results illuminate the role of free radicals in human RA.     

Lipopolysaccharide accelerates collagen‐induced arthritis in association with rapid and continuous production of inflammatory mediators and anti‐type II collagen antibody

Collagen‐induced arthritis (CIA) is an animal model for rheumatoid arthritis (RA). Lipopolysaccharide (LPS) is known to accelerate CIA; however, the pathogenetic mechanisms are not yet fully understood. In this study, type II collagen (CII)‐immunized mice were found to have marked increases in degree of expression of mRNA of inflammatory mediators such as tumor necrosis factor alpha (TNF‐α), interleukin (IL)‐1β, and macrophage inflammatory protein‐2 (MIP‐2) in their arthritic paws and of serum anti‐CII antibody concentration before the onset of arthritis induced by LPS injection. The gene expression was rapid and continuous after direct activation of nuclear factor κB. The amounts of mRNA of TNF‐α, IL‐1β, and MIP‐2, as well as of matrix metalloproteinases and the receptor activator of nuclear factor κB ligand, increased with the development of arthritis, correlated positively with clinical severity and corresponded with histopathological changes. Moreover, anti‐TNF‐α neutralizing antibody inhibited the development of LPS‐accelerated CIA and a single injection of recombinant mouse TNF‐α induced increases in anti‐CII antibody concentrations, suggesting TNF‐α may contribute to the development of arthritis by both initiation of inflammation and production of autoantibodies. These data suggest that exacerbation of RA by LPS is associated with rapid and continuous production of inflammatory mediators and autoantibodies.     

T cells that are naturally tolerant to cartilage-derived type II collagen are involved in the development of collagen-induced arthritis

The immunodominant T-cell epitope that is involved in collagen-induced arthritis (CIA) is the glycosylated type II collagen (CII) peptide 256-270. In CII transgenic mice, which express the immunodominant CII 256-270 epitope in cartilage, the CII-specific T cells are characterized by a partially tolerant state with low proliferative activity in vitro, but with maintained effector functions, such as IFN-γ secretion and ability to provide B cell help. These mice were still susceptible to CIA. The response was mainly directed to the glycosylated form of the CII 256-270 peptide, rather than to the nonglycosylated peptide. Tolerance induction was rapid; transferred T cells encountered CII within a few days. CII immunization several weeks after thymectomy of the mice did not change their susceptibility to arthritis or the induction of partial T-cell tolerance, excluding a role for recent thymic emigrants. Thus, partially tolerant CII autoreactive T cells are maintained and are crucial for the development of CIA.     

Gene expression dynamics in deer antler: mesenchymal differentiation toward chondrogenesis

Annual re-growth of deer antler represents a unique example of complete organ regeneration. Because antler mesenchymal cells retain their embryonic capacity to develop into cartilage or bone, studying antler development provides a natural system to follow gene expression changes during mesenchymal differentiation toward chondrogenic/osteogenic lineage. To identify novel genes involved either in early events of mesenchymal cell specialization or in robust bone development, we have introduced a 3 K heterologous microarray set-up (deer cDNA versus mouse template). Fifteen genes were differentially expressed; genes for housekeeping, regulatory functions (components of different signaling pathways, including FGF, TGFβ, Wnt), and genes encoding members of the Polycomb group were represented. Expression dynamics for genes are visualized by an expression logo. The expression profile of the gene C21orf70 of unknown function is described along with the effects when over-expressed; furthermore the nuclear localization of the cognate protein is shown. In this report, we demonstrate the particular advantage of the velvet antler model in bone research for: (1) identification of mesenchymal and precartilaginous genes and (2) targeting genes upregulated in robust cartilage development. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

麋鹿鹿角脱落、群主更替、产仔的年节律及其环境影响因子

本文在2014—2016年三个冬季(12月—翌年2月)收集了北京南海子麋鹿苑半散放麋鹿自然脱落的角,并观察和记录了2015—2017年发情期(5—9月)群主更替和2016—2018年产仔期(3—7月)麋鹿幼仔出生情况,结合2014—2018年年平均气温、季平均气温、月平均气温、年降雨量、雨季开始时间、种群密度等环境因子,对鹿角脱落、群主更替、产仔等繁殖特征的年节律及其环境影响因子进行了研究。结果表明：1)麋鹿鹿角脱落、群主更替、产仔的年节律均存在年际差异。2)鹿角脱落时间为12月开始,1月下旬或2月上旬结束。3)发情期为5月下旬或6月上旬开始,9月上旬结束;2015—2017年发情期时间有延长的趋势。4)产仔期为3月中旬或4月中旬开始,5月下旬或7月下旬结束。5)麋鹿鹿角脱落、群主更替、产仔的年节律存在明显的同步关系,其中鹿角脱落开始时间、鹿角脱落高峰期、鹿角脱落结束时间、第一次发情期开始时间、群主更替高峰期、产仔期开始时间、产仔高峰期、产仔期结束时间与前一年度比较均出现同步提前的现象。6)鹿角脱落年节律存在随着12月平均气温升高而提前的现象;产仔期开始时间和产仔高峰期存在随着前一年9月平均气温的升高而提前的现象。7)鹿角脱落年节律表现出随着年降雨量的增多而提前的现象;第一次发情期开始时间、群主更替高峰期的年节律表现出随着前一年度年降雨量的增多而提前的现象。8)麋鹿鹿角脱落、群主更替、产仔的年节律均不存在随着种群密度升高或降低而提前或延迟的现象。麋鹿繁殖特征的年节律是一个复杂的过程,受气候、营养、种群密度、纬度等环境因子的影响。     

Suppression of collagen arthritis with antibodies to an arthritogenic, oligoclonal T cell line.

Rats immunized with type II collagen (CII) develop an immunologically mediated polyarthritis. T cells have been implicated in the pathogenesis of this model since they can adoptively transfer the disease. A CII-specific T cell line (VA), consisting of three distinct clones by Southern blot analysis, has been shown to be arthritogenic. Antibodies specific for this line were generated by immunizing rabbits. In an attempt to prevent collagen-induced arthritis (CIA), Louvain rats were injected with 1 ml of anti-VA ip on Days -1, +1, +3 and 0.5 ml on Day +5 (early treatment). To evaluate its effect on existing disease, rats received anti-VA on the day of arthritis onset and subsequently on 4 successive alternate days using the same dosage protocol (late treatment). Control rats received no therapeutic injections or were administered normal rabbit serum. All rats were immunized with CII on Day 0 to induce CIA. Rats administered antibodies using the early anti-VA treatment protocol had a significantly diminished incidence of arthritis compared to controls. Established arthritis was significantly diminished compared to controls in rats given the late anti-VA treatment. In both protocols, radiographic evidence of joint destruction was significantly reduced compared to controls. T cell phenotyping using flow cytometry analysis demonstrated that the anti-VA antibody therapy selectively eliminated a small subset of T cells since there was little difference in total T cell counts in the experimental versus control groups. Delayed type hypersensitivity and IgG antibody titers to CII were minimally decreased in the experimental versus control group. These results suggest that antibodies raised to an oligoclonal arthritogenic T cell line can suppress collagen arthritis. This may have implications with respect to 1) the size of the T cell receptor repertoire involved in the pathogenesis of collagen arthritis and 2) immunospecific protocols for CIA and other autoimmune diseases.     

Juvenile-to-Adult Antler Development in White-Tailed Deer in South Texas

Abstract: Past studies using penned deer provide conflicting results on the age when reliable predictions about antler growth potential in white-tailed deer (Odocoileus virginianus) can be made. We captured wild whitetail males via aerial net gun on 12 ranches in 5 counties in south Texas, USA, from 1999 to 2007 to determine if a reliable juvenile-to-adult relationship in antler development existed. We individually marked and released captured animals at the trap site after we took antler and body measurements. We recaptured marked animals as possible in subsequent years or until we obtained final measurements after legal harvest. Amount of growth in the first set of antlers in whitetail males was a poor predictor of antler growth at maturity. By 4.5 years of age there were no differences (P > 0.05) in antler measurements regardless of the amount of development of the first set of antlers at 1.5 years. We concluded culling of yearling males based on number of antler points would have little positive effect on overall antler quality in future years.     

Resistance to collagen-induced arthritis in SHPS-1 mutant mice

SHPS-1 is a transmembrane protein that binds the protein tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region and is abundantly expressed on dendritic cells and macrophages. Here we show that mice expressing a mutant form of SHPS-1 fail to develop type-II collagen (CII)-induced arthritis (CIA), a model for rheumatoid arthritis in humans. Histological examinations of the arthritic paws from immunized wild-type mice revealed that cartilage was destroyed in association with marked mononuclear cell infiltration, while only mild cell infiltration was observed in immunized SHPS-1 mutant mice. Consistently, the serum levels of both IgG and IgG2a specific to CII and of IL-1β in immunized SHPS-1 mutant mice were markedly reduced compared with those apparent for wild-type mice. The CII-induced proliferation of, and production of cytokines by, T cells from immunized SHPS-1 mutant mice were reduced compared to wild-type cells. These results suggest that SHPS-1 is essential for development of CIA.     

LFA-1基因敲出鼠胶原诱导风湿性关节炎发病率及程度的降低

淋巴细胞功能相关抗原（LFA-1）属于黏附分子家族,在细胞相互作用中发挥重要作用。通过观察LFA-1基因敲除小鼠的胶原诱导关节炎(CIA)发病率、放射线学及组织学变化,探讨LFA-1分子在CIA发病中的作用。实验采用100μg的二型胶原(CII)加弗氏完全佐剂充分混合,在LFA-1基因敲除小鼠及正常对照组小鼠尾根部皮内注射,21天后重复免疫一次,随后进行发病率、放射线学及组织学分析。研究结果显示,CII免疫后,正常对照组小鼠平均发病率为57%,临床可见明显的放射线及组织学的异常变化。而LFA-1基因敲除小鼠无发病,放射线及组织学检查亦无明显异常改变。上述结果提示LFA-1在胶原诱导的关节炎发病中起重要作用。     

Immunogenetics of collagen-induced arthritis in rats. Both MHC and non-MHC gene products determine the epitope specificity of immune response to bovine and chick type II collagens.

Seven inbred, RT1-congenic rat strains were immunized with native bovine (BII), porcine (PII), or chick (CII) type II collagen and observed for onset, incidence, and severity of arthritis. Clinical results were compared with IgG reactive with native rat type II collagen (RII) and the purified, renatured cyanogen-bromide peptides of BII, CII, or RII. Immunodominant responses to CB11, CB9,7, and CB12 of RII were identified. Secondary responses to CB8 and CB10 also occurred. Reproducible patterns of peptide reactivity were defined in each strain and reflected both RT1 and non-RT1 genotypes plus the species of immunizing collagen. BN non-RT1 gene products moderated clinical arthritis but increased the levels of reactivity to CB11 in three strains carrying RT1l,n,av1 haplotypes. WF (RT1u) rats were susceptible to collagen-induced arthritis (CIA) and developed very high levels of autoantibodies with dominant responses to rat CB11 after CII injections and to rat CB11 and CB9,7 after BII injections. DA (RT1av1) rats developed the most severe arthritis but had only moderate (total) levels of anti-RII IgG: a broad response to CB11, CB10, and CB9,7 after CII injections but predominantly to CB12 and CB9,7 after BII injections. Three RT1n strains--DA.1N(BN), WF.1N(MAXX), and BN--were resistant to BII-induced CIA but developed mild arthritis after immunization with CII. After BII: BN IgG reacted with CB9-7, CB11, and CB12; DA.1N and WF.1N IgG reacted with CB9,7 and CB12. After CII: BN IgG reacted broadly with CB11, CB9-7, CB12, and CB8; WF.1N IgG reacted to CB9-7, CB11, CB8, and CB12; DA.1N IgG reacted with CB8, CB11, and CB9-7. Thus, selective induction of CIA in BN, WF.1N, and DA.1N rats by CII correlated with serum IgG reactivity to rat CB11, but overall strain results identified no single cyanogen-bromide peptide as expressing the sole "arthritogenic" epitope in CIA.     

Comparative evaluation of antioxidant, nitrite scavenging, and antitumor effects of Antrodia camphorata extract

The effects of decoctions prepared from Antrodia camphorata on antioxidant, nitrite scavenging, and antitumor activities were investigated. Glutathione (GSH) production was 18.2 μM/g of rat liver under the influence of a methanol extract, a result similar to with the effect of silymarin administration. GSH peroxidase activity was about 2.0-fold higher than with silymarin administration. Superoxide dismutase activity was 18.9 U/mg protein, about 2.5-fold higher than the control group. The hot water extract (1000 μg/mL) showed the highest nitrite scavenging activity at 98.1%, similar to those observed with BHA and vitamin E. Among a variety of human cancer cell lines, when the concentration of hot water extract was increased from 31 to 500 μg/mL, the viability of Hep3B cell was decreased from 100 to 60.7%. On the other hand, in the case of methanol extract, it was decreased from 98.4 to 10.0%. These results supported the conclusion that the antioxidant, nitrite scavenging, and antitumor activities of this A. camphorata methanol extract indicate a potential source for the development of various health supplements and pharmaceutical and nutraceutical applications.     

Suppression of collagen‐induced arthritis by oral administration of transgenic rice seeds expressing altered peptide ligands of type II collagen

Rheumatoid arthritis (RA) is an autoimmune disease associated with the recognition of self proteins secluded in arthritic joints. We previously reported that altered peptide ligands (APLs) of type II collagen (CII256‐271) suppress the development of collagen‐induced arthritis (CIA). In this study, we generated transgenic rice expressing CII256‐271 and APL6 contained in fusion proteins with the rice storage protein glutelin in the seed endosperm. These transgene products successfully and stably accumulated at high levels (7–24 mg/g seeds) in protein storage vacuoles (PB‐II) of mature seeds. We examined the efficacy of these transgenic rice seeds by performing oral administration of the seeds to CIA model mice that had been immunized with CII. Treatment with APL6 transgenic rice for 14 days significantly inhibited the development of arthritis (based on clinical score) and delayed disease onset during the early phase of arthritis. These effects were mediated by the induction of IL‐10 from CD4⁺ CD25^? T cells against CII antigen in splenocytes and inguinal lymph nodes (iLNs), and treatment of APL had no effect on the production of IFN‐γ, IL‐17, IL‐2 or Foxp3⁺ Treg cells. These findings suggest that abnormal immune suppressive mechanisms are involved in the therapeutic effect of rice‐based oral vaccine expressing high levels of APLs of type II collagen on the autoimmune disease CIA, suggesting that the seed‐based mucosal vaccine against CIA functions via a unique mechanism.     

Fighting behaviour in territorial male roe deer <Emphasis Type="Italic">Capreolus capreolus</Emphasis>: the effects of antler size and residence

In all areas where they have been studied, male roe deer are believed to have a territorial mating system, although few quantitative studies have been conducted and there remains considerable debate about the function of male roe deer territories. We observed 139 aggressive interactions between male roe deer in Storfosna Island (Norway) during one territorial season (March–August). We recognised seven rank levels of escalation according to the potential danger of the behaviour. On the basis of the number of escalation levels included in the interactions, the complexity of the fights was also scored. We recorded the presence of other individuals during the interaction, the age, the antler size, the territorial status and the residency status of the two contestants and tested how these variables affected escalation, complexity and outcome of the fights. Most of the interactions ended with low levels of escalation, and physical contact occurred only in fights between two territorial bucks. The escalation was also affected by the difference in antler size index (the bucks escalated more when the difference in antler size was smaller) and increased with an increasing number of female deer present during the interaction. The resident buck won in 81% of the fights. When it drew or lost, it was generally both inferior in age and antler size, and the duration and escalation of the interactions were higher. However, even when a fight was lost, no territory loss occurred. These results are consistent with the evolutionary game theory and the proposed low risk–low gain strategy of roe deer bucks.     

Tolerance induction by a poorly arthritogenic collagen II can prevent collagen-induced arthritis

Collagen type II (CII)-induced arthritis (CIA) can be induced in 78% of B10.RIII mice (H2r) by intradermal (id) immunization with CII of bovine origin in complete Freund's adjuvant (CFA), whereas immunization with CII of chick origin induces arthritis in less than 5% of these mice. Nevertheless, tolerization of B10.RIII mice with intravenously injected chick CII renders the animals resistant to induction of CIA by immunization with bovine CII. Such tolerization can be achieved either by intravenous injection of 500 micrograms chick CII 1 week prior to immunization with bovine CII in CFA or by such an intravenous injection of chick CII 2 weeks after immunization with bovine CII in CFA. Postimmunization treatment results in a significant decrease in the concentration of antibody to bovine CII. Preimmunization administration of chick CII causes a marked decrease in the antibody reactive with chick CII without a significant effect on the anti-bovine CII antibody concentration. In DBA/1 mice, a strain in which both bovine CII and chick CII can induce a high incidence of the disease, intravenous injection of bovine CII can also prevent arthritis induced by chick CII, even when given 7 or 14 days after immunization. The fact that chick CII as tolerogen is quite effective in preventing arthritis in B10.RIII mice, while as immunogen it is very ineffective in inducing arthritis in this strain, may be interpreted as evidence for interaction between different epitopes on CII in the pathogenesis of CIA.     

Comparison of Effects of Shed Antler Hunting and Helicopter Surveys on Ungulate Movements and Space Use

Shed antler hunting (i.e., collecting cast cervid antlers) has increased in popularity during the past decade, but little is known about how this recreational activity affects ungulate movements and space use. We placed geographic positioning system (GPS)-collars on 133 female and male bighorn sheep (Ovis canadensis), bison (Bison bison), and mule deer (Odocoileus hemionus) to quantify their movements and space use during shed antler hunts compared with those behaviors during helicopter surveys in Utah, USA, from 2012 to 2015. For each species, we calculated means and 95% confidence intervals for distance moved during 90-minute segments (16 points/day) pre-event (control, 7 consecutive days prior to event), event (1–2 days), and post-event (7 consecutive days after event) for shed antler hunts and helicopter surveys. We also compared use of space for each species during these events. Female bighorn sheep did not increase distance moved or substantially change space use during shed antler hunts and helicopter surveys. Male bighorn sheep increased distance moved 41% on average during shed antler hunts and by 2.02 times during helicopter surveys but did not change space use during those events. Female bison increased distance moved 15% on average during shed antler hunts and 30% during helicopter surveys. Mule deer increased distance moved and altered space use the most during shed antler hunts; females increased distance moved 97%, and 54% of females moved a mean distance of 742 ± 642 (SD) m (range = 9–3,778 m) outside of their home ranges during those hunts for a mean of 9.2 ± 9.4 hours (range = 1.5 to 41 hr). Male mule deer increased distance moved by 2.10 times on average during shed antler hunts, and 82% of males moved a mean distance of 1,264 ± 732 m (range = 131–3,637 m) outside of their home ranges during those hunts for a mean of 12.6 ± 7.6 hours (range = 4.5–33 hr). Our results provide timely information about how legal shed antler hunting affects movements and space use of female and male ungulates, especially mule deer, and can guide the conservation of ungulate populations and their habitat. © 2021 The Wildlife Society.     

Production of murine collagen-induced arthritis using Klebsiella pneumoniae O3 lipopolysaccharide as a potent immunological adjuvant.

Collagen-induced arthritis (CIA) was produced in mice with non H-2q and H-2r haplotypes by repeated immunization of porcine type-II collagen (CII) together with Klebsiella O3 lipopolysaccharide (KO3 LPS) as an immunological adjuvant. Histological changes that appeared in joints of repeatedly immunized mice were characterized by destruction of normal joint structure, synovial hyperplasia with proliferation of synovial cells, and infiltration of inflammatory cells. No such lesions were produced in mice receiving repeated injections of CII alone or KO3 LPS alone. Development of the humoral antibody and the delayed-type hypersensitivity to CII was exclusively found in mice immunized with the mixture of CII and KO3 LPS. It was therefore suggested that arthritis lesions induced by repeated immunization with the mixture of CII and KO3 LPS might be caused by an autoimmune mechanism, and that the experimental model might be useful for characterization of human rheumatoid arthritis (RA).