Why is overproduction in rabbits necessary

However, for a long time, it is not clear whether apoCIII was directly involved in the pathogenesis of atherosclerosis because mouse models failed to provide a clear answer Yan et al. Yang et al. Recently, we have shown that that genetic deletion of the apoCIII gene in KO rabbits significantly accelerates catabolism of TG-rich lipoproteins in the liver and apoCIII deficiency leads to the resistance of KO rabbits to a cholesterol diet-induced hyperlipidemia and inhibits atherosclerosis Yan et al.

These results indicate that therapeutic inhibition of apoCIII expression may become a novel strategy for the treatment of hyperlipidemia and atherosclerosis.

ApoE is a ligand for both LDL receptor and LRP and plays an important role in the catabolism of remnant lipoproteins in the liver and genetic deficiency of apoE is a cause of human type III hyperlipoproteinemia Mahley, ; Mahley et al. Deletion of apoE in mice even on a normal chow diet exhibited hyperlipidemia along with spontaneous aortic atherosclerosis Plump et al. Even though different techniques were adopted, apoE KO rabbits generated by these two methods exhibit the same phenotypes Niimi et al.

Because plasma levels of cholesterol in apoE KO rabbits on a normal diet are not high to be atherogenic, there are not spontaneous atherosclerosis, which is different from apoE KO mice.

Recently, we found that apoE KO rabbits are highly susceptible to a cholesterol diet-induced atherosclerosis. Therefore, apoE KO rabbits will serve as a new model for human hyperlipidemia. In humans, genetic deficiency of LDL receptor functions causes severe hypercholesterolemia and atherosclerosis at early ages, called familial hypercholesterolemia FH.

Cholesteryl ester transfer protein CETP is a glycoprotein that transfers plasma lipids between HDLs and apoB-containing particles therefore plays an important role in lipoprotein metabolism. Taking this advantage, Zhang et al. These results indicate that genetic ablation of CETP gene inhibits the development of atherosclerosis in cholesterol-fed rabbits.

However, its physiological functions are largely unknown compared with apoAI. We first made Tg rabbits expressing human apoAII gene and found that hepatic expression of human apoAII inhibits cholesterol diet-induced atherosclerosis Wang et al. In the latest study, we found that apoAII KI rabbits showed consistently lower TG and higher HDL-cholesterol levels and developed significantly less aortic atherosclerosis on a cholesterol diet Koike et al.

Although genetically modified rabbits are an important experimental model in cardiovascular research, they should not be simply used as a substitute of mice and rats, as discussed above.

Because rabbits are more expensive, require larger space, and need more time to breed compared with mice, the generation of genetically modified rabbits should be carefully planned to solve those specific problems that cannot be well-examined in other experimental animal models, such as the development of lipid-lowering drugs Niimi et al.

However, off-target effects in these animals remain a concern as the genome editing is extremely productive and efficient.

So far, almost all studies claimed that off-targets in genetically modified rabbits through genome editing are either none or negligible as comprehensively discussed in the recent review Song J. It can be expected that more and more genetically modified rabbits will be made and used in a variety of medical sciences which will certainly expand our knowledge to explore new mechanisms of human diseases. Genome editing technique may eventually replace the pronuclear microinjection for the generation of Tg rabbits.

Finally, the preservation of valuable strains of genetically modified rabbits is an urgent task with increased number of rabbit models produced. In this aspect, various procedures for cryopreservation of rabbit sperm Vicente and Viudes-de-Castro, ; Dalimata and Graham, ; Nishijima et al.

In the future, it may be necessary to establish an international rabbit bio-resource center or sperm and embryo bank to stock and share valuable rabbit models worldwide.

All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We would like to thank the following people for their contribution to this project. Aigner, B. Tyrosinase gene variants in different rabbit strains. Mammalian Genome. Cryopreservation of rabbit zygotes. Human Reprod. Bers, D. Cell Cardiol.

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Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome. Carneiro, M. The genomic architecture of population divergence between subspecies of the european rabbit. PLoS Genet. Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication.

Chen, M. Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy MPL syndrome in rabbit. Chen, Y. Macrophage-derived MMP-9 enhances the progression of atherosclerotic lesions and vascular calcification in transgenic rabbits. Cell Mol. Chesne, P. Cloned rabbits produced by nuclear transfer from adult somatic cells. Christian, M. Genetics , — Dalimata, A. Cryopreservation of rabbit spermatozoa using acetamide in combination with trehalose and methyl cellulose.

Theriogenology 48, — Deng, J. The disrupted balance between hair follicles and sebaceous glands in Hoxcablated rabbits. Ding, Y. Hypertriglyceridemia and delayed clearance of fat load in transgenic rabbits expressing human apolipoprotein CIII. Transgenic Res. Duverger, N. Inhibition of atherosclerosis development in cholesterol-fed human apolipoprotein A-I-transgenic rabbits.

Circulation 94, — Transgenic rabbits expressing human apolipoprotein A-I in the liver. Fan, J. Assembly of lipoprotein a in transgenic rabbits expressing human apolipoprotein a. Transgenic rabbit models for biomedical research: current status, basic methods and future perspectives.

Principles and applications of rabbit models for atherosclerosis research. Increased expression of apolioprotein E in transgenic rabbits results in reduced levels of very low density lipoproteins and an accumulation of low density lipoproteins in plasma.

Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine. Transgenic rabbits expressing human apolipoprotein a develop more extensive atherosclerotic lesions in response to a cholesterol-rich diet. Overexpression of lipoprotein lipase in transgenic rabbits inhibits diet-induced hypercholesterolemia and atherosclerosis. Overexpression of hepatic lipase in transgenic rabbits leads to a marked reduction of plasma high density lipoproteins and intermediate density lipoproteins.

Cholesterol-fed and transgenic rabbit models for the study of atherosclerosis. Transgenic rabbits as therapeutic protein bioreactors and human disease models. Flisikowska, T.

Efficient immunoglobulin gene disruption and targeted replacement in rabbit using zinc finger nucleases. Gao, S. Overexpression of cholesteryl ester transfer protein increases macrophage-derived foam cell accumulation in atherosclerotic lesions of transgenic rabbits. Mediators Inflamm. Geurts, A. Knockout rats via embryo microinjection of zinc-finger nucleases.

Science Goldstein, J. Defective lipoprotein receptors and atherosclerosis. It can take up to two months for the cecal flora to completely return to normal, particularly if the rabbit has had abnormal cecotropes for weeks or months prior to treatment. I advise my clients to never feed any high-carbohydrate especially grain-based foods again.

If pellets are to be eventually introduced, I recommend that only grass-hay-based not alfalfa-based pellets be fed on a very limited basis; the food should be devoid of grains. Some rabbits can be successfully fed small amounts of dried or fresh fruit if they are introduced gradually, with the cecotropes remaining normal. However, if soft cecotropes are produced again within twelve to twenty-four hours of the introduction of any food into the diet, immediately discontinue that food.

As already noted, a gradual change in pellet amount or kind alfalfa-based to grass-hay-based may have to be done gradually to prevent hepatic lipidosis. Treatment for the early stage of cecal hypomotility slowdown leading to impaction is much the same as for ileus, the cessation of GI tract movement. Unfortunately, the rabbit may not always be brought to the animal hospital early in the condition.

Bill Guerrera, who treats many rabbits from the Colorado House Rabbit Society, shares his experience:. At first, the rabbit may act very normal and is eating and drinking. Contents of the cecum are normally semifluid. So when I palpate doughy contents in the cecum instead, my diagnostics may include radiographs and blood work to assess the severity of the situation. I also want to rule out other systemic illness or disease. Before the rabbit is dismissed from the hospital, sterile fluids are given subcutaneously to help soften the mass and get it moving.

I work out a treatment protocol for the caregiver that includes additional hydration if necessary, and some caregivers are skilled in giving fluids at home. Current research indicates that return to health hinges on fluids and fiber. Prokinetics motility drugs may be considered, though scientific trials are lacking; opinions on which drugs are most effective vary.

Some veterinarians may prescribe probiotics for rabbits on antibiotics for extended periods of time, but the efficacy of presently available probiotics is currently unknown. Because cecal impaction is a serious threat, I want to see the rabbit respond to treatment within twenty-four hours. If it empties and the flora balance is restored, the prognosis for the rabbit is very good. I encourage the client to give the recovering rabbit gentle tummy massages and to allow him to be active.

Cecal impaction is extremely serious. Though the rabbit may look fat, due to abdominal distension, he or she may be very emaciated and most likely unable to absorb the nutrition needed to maintain health. Acute dehydration may lead to additional problems.

When a rabbit is severely dehydrated, the peripheral circulation shuts down in order to maintain circulation to internal organs and the brain. That means that subcutaneous fluids are not absorbed quickly enough to do much good.

Administration by IV intravenous, by vein or IO intraosseous, into the bone marrow, e. An analgesic for pain will also be required. It is an injectable that can be given orally if mixed with something palatable. However, the drug is not without significant risks, as Dr. In addition, the drug can destroy the stomach lining and damage the kidneys, especially in a dehydrated rabbit. When there is dehydration and shutdown, buprenorphine an injectable morphine derivative may be more appropriate.

Meloxicam works well in well-hydrated rabbits. This negative effect on prostaglandins, a group of hormone-like substances, is an important consideration. Cecal impaction does not mean a rabbit cannot recover.

Fluids are critical to the working of the cecum, so hydration is the key. Fiber is second in importance. Cecal contents have to be softened up, and then fiber helps get things moving again. I like to monitor them closely because once the cecum has been stretched, it potentially loses tone and is more flaccid than it should be.

Rabbits who have had cecal impactions in the past are more likely to develop problems in the future: the cecum may fill up again. Proper nutrition is a must for these rabbits to decrease the probability of recurrence. There are times when the cecum does not empty and the rabbit is in a life-threatening situation.

Guerrera offers:. I become very concerned when a rabbit is not responding to treatment and starts to have diarrhea, lethargy, and weight loss. Sometimes the cecum will not empty. The decision to go to surgery is never easy. For most veterinarians, surgery into the cecum is the last resort; thus, it is carried out primarily on critically ill patients. The cecum itself is a paper-thin bag of bacterial contamination and does not hold sutures well. Even if surgery is successful, there is always a risk of postoperative sepsis [life-threatening internal infection].

The technically difficult procedure on a critically ill patient equals a poor success rate. If the rabbit does survive the surgery, there is a chance the cecum may not return to normal function. I would also have concern about the long-term prognosis for the rabbit. A rabbit who has any signs of cecal motility disorder should be checked by a veterinarian experienced with rabbits to make sure there is no underlying disease. The information contained in the sub-section immediately below applies to the whole of this section, though a veterinarian may provide specific guidelines for feeding pellets and leafy greens, depending on the condition of a rabbit.

When a bunny has soft, poorly formed cecotropes, it is recommended that caregivers discuss the daily feeding regimen with a veterinarian who is knowledgeable about the appropriate diet before making major changes. If the rabbit who has gooey cecotropes grazes freely on hay throughout the day, Dr. Angela Lennox, who has practiced exotic animal medicine exclusively for more than twenty years and is past president of the Association of Exotic Mammal Veterinarians, concurs:.

Hay drives the gastrointestinal tract. Brown indicates:. Rabbits who do not freely graze on hay can be maintained on grass-hay-based pellets and leafy greens. However, some rabbits who are producing abnormal cecotropes will not completely return to normal if fed any pellets, even grass-hay-based.

This may be due to a starch or protein content in the pellet that is still too high for that individual rabbit. Caregivers can usually entice their rabbits to eat hay by offering variety and interest, perhaps sprinkling on an aromatic cooking herb for example. Though long-fiber hay is preferable, timothy-based hay cubes are an option. Offering a variety of grass hay timothy, orchard, brome, oat may create interest and is healthiest for most adult rabbits.

Note that alfalfa is often mixed in with orchard grass, so it is wise to ask about content before purchasing. Good quality hay should be fed in long-fiber form i. If you have a rabbit who refuses hay, query rabbit-savvy people about their successes in getting a rabbit to eat it. For those rabbit guardians who are concerned that leafy vegetables may be the cause of abnormal cecotropes, Dr.

Brown advises that true vegetable intolerance is rare. Lennox offers additional explanation:. However, problems are most often caused by previous damage from chronic inappropriate diet and lack of exercise.

The focus should be on coarse fibrous plant materials [grass hay]. Read our supplemental article on hock injury for more detailed information if your rabbit has problems with hock injury. Ears: Ear wax from the outer ear can be removed from the outer ear with a cotton swab. Be careful not to push on wax in the canal, and no not attempt to reach deep into the ear canal. Your vet may recommend a variety of wax removal products as need be for your bunny.

Nail Trims: Check the nails once a week when grooming and trim the nails whenever they get a bit long. I find it is better to do frequent trims even if you are only trimming a sliver off than wait until the nail is quite long and trying to judge how much to remove. Rabbit nails can grow to be very long and will be uncomfortable for the rabbit. Allowing nails to grow too long may cause toe or nail injuries, foot injury and gait issues for your bunny.

How to trim bunny nails: Place the bunny in a comfortable position where you can easily reach their feet. We tend to do nail trims with the rabbit laying on our laps with feet up towards us, or having the rabbit in a standing potion on a table where the rabbit is comfortable and we can pick up one foot at a time to trim the nails. Some people also use a towel to wrap their rabbit to keep bunny secure. Then they bring out one foot at a time to trim. If the rabbit has light colored nails their nails will be easier to trim as you can see where the blood supply or Quick starts and can trim below that line.

Dark colored nails are harder to see through and therefore, you may want to use a back light flashlight which will allow you to see the nail quick. Some people use a touch spring back approach and I do not recommend that. It does work for very experienced people. Trimming baby rabbit nails: Baby rabbit nails are very sharp and we recommend using an emery board to gently trim tips of their nails. People are often afraid to clip nails for fear that they will trim incorrectly and cause the rabbit to bleed.

So be careful in trimming nails and always have on hand a septic powder product in case you make a mistake and the rabbit's nail bleeds. You can purchase a product called Kwik Stop to keep on hand for this problem. If the nail bleeds apply a bit of powder to the nail an also apply pressure for a minute. Your veterinarian or staff at any Rabbit Haven adoption show or event will also clip nails for you. Rabbit nails need to be trimmed about every month.

Eyes: Checking your rabbit's eyes for any redness or items like hay or fur that may be in the eye or on the eye rim is a part of grooming. You may use eye wash to remove material from the eye or move it to the edge where you may use a cotton ball to wipe it away. Of course never touch the actual eye. Some people use a special comb to groom fur back from the eye on rabbits that have heavy fur around their eyes.

Mites, fleas and ticks and other skin disease may all damage your rabbit's skin and impact their health. Signs of parasites: Black fleas are usually seen near the head, face or genital area. Ticks may be found anywhere on the rabbit. Mites appear as dandruff and may cling to fur and skin. A tick is an oval shaped parasite that may be crawling on rabbit's fur or attached to your rabbit's skin.

Watch your rabbit for signs of these parasites. Symtoms of these parasites include itching, scratching, flaky skin with bald patches or dandruff like materials near the skin of your rabbit and on the fur close to their skin. Ear mites are more readily observed as they quickly invade the ear, and you will notice the dark dried debris they leave behind. This is extremely irritating to your rabbit, so it is hard to miss.

Ear mites are highly destructive and may damage your rabbit's ears. Seek vet care immediately. There are many different types of skin issues that may occur so having regular vet care will help you keep your rabbits skin free of decease and help your rabbit be healthy.

Fleas and Mites: Even when our rabbit are housed indoors they may get fleas, ticks or mites. We can also accidently carry in parasites on our shoes and clothing. We are not fully ready to answer questions in a timely manner as we are not officially open, but we will do our best.

The subject of intentional breeding or meat rabbits is prohibited. The answers provided on this board are for general guideline purposes only. The information is not intended to diagnose or treat your pet. What are we about? Please read about our Forum Culture and check out the Rules. How long is it okay to assume that a rabbit is overproducing cecals without it being a health problem???

I know Simba had this problem before and he was fine…. We took him to the vet and within a few days he was fine. She gave him some Metacam because she thought something down below in his tummy area felt sore. She believed he got a kind of back-up in his system and so the overproduction of cecals was due to his body finally pushing them all out at once making it hard for him to keep up and causing the poopy butt type production.

No pooopy butt on anyone this time we checked everyone.