Monitoring of blood gas parameters and acid-base balance of pregnant and non-pregnant rabbits (Oryctolagus cuniculus) in routine experimental conditions.

Blood gas parameters and acid-base balance values were determined in adult pregnant New Zealand rabbits (Oryctolagus cuniculus) in standard laboratory housing conditions and during anaesthesia with an association of ketamine-chlorpromazine, administered before surgical procedures. All the variables were also studied in adult non-pregnant female, used as controls. No differences in pH, sO2c, O2Hb, COHb, sO2m and a-vDO2 were found between pregnant and non-pregnant rabbits in physiological conditions and during anaesthesia. Ketamine-chlorpromazine and pregnancy seemed to change the other parameters used to assess the acid-base balance and the oxygenation conditions. Anaesthesia affected only Hb, O2Ct, O2Cap, CcO2 and P50. The additive effect of pregnancy and anaesthesia modified pCO2, pO2, HCO3-, TCO2, BEb, SBC, BEecf, A-aDO2, RI, MetHb, RHb, CaO2 and CvO2. The patterns described are close to those of other species, suggesting the New Zealand rabbit might be a reliable animal model for monitoring selected variables.     

The Dutch-Belted rabbit: an alternative breed for developmental toxicity testing

BACKGROUND: Historical control data play a crucial role in the interpretation of observations made from developmental and reproductive toxicity studies. METHODS: In our effort to develop the Dutch‐Belted rabbit as an alternative breed of rabbit for testing of small molecule pharmaceuticals, data collected from 236 untreated pregnant Dutch Belted rabbits are summarized and compared to data collected from 350 untreated pregnant New Zealand White Rabbits. RESULTS: The data presented include mean maternal body weight and food consumption values, mean maternal hematological and serum biochemical values collected during gestation, maternal reproductive (laparotomy) parameters collected at cesarean section, and incidences of spontaneous fetal morphological alterations collected during 1999–2002. Due to their smaller size the use of this breed of rabbit would require approximately 40% less drug than studies conducted with New Zealand White rabbits. Because the Dutch‐Belted rabbit is pigmented this breed also offers the ability to test the potential effects of various xenobiotics on melanocyte development and to evaluate the potential sequela of drugs that have a propensity to bind melanin in the skin and pigmented retinal epithelium. CONCLUSIONS: Based on these data, the Dutch‐Belted rabbit is considered to be a practical alternative to use of the New Zealand White rabbit for these types of studies. Birth Defects Res B 68:439–448, 2003. © 2003 Wiley‐Liss, Inc.     

Lymphosarcoma with lymphoblastic leukemia in a New Zealand white rabbit.

An 8 to 10-week-old female New Zealand white rabbit, Oryctolagus cuniculus, which exhibited clinical signs of anorexia, depression, and torticollis was found to have lymphosarcoma with lymphoblastic leukemia. The multiple visceral involvement with neoplastic lymphoid cells observed in this animal was similar to previously reprted cases of lymphosarcoma in the rabbit. An unusual finding was the occurrence of lymphoblastic leukemia since lymphosarcoma in the rabbit has previously been reported as aleukemic.     

A comparative study of nerve healing in adult, neonatal, and fetal rabbits.

This experiment quantitatively compared the human equivalent of a nerve repair following surgical division in the fetal, adult, and early childhood period of development using a rabbit as an experimental animal model. Twelve time-dated pregnant New Zealand White rabbits at 24 days' gestation (term = 31 days) underwent hysterotomy; one hind limb was delivered through the uterine opening. The sciatic nerve was divided and repaired by primary neurorrhaphy using two 11-0 epineural sutures. Sciatic nerve repair was also performed in 10 neonatal and 10 adult New Zealand White rabbits. Following repair, each group was assessed using electromyography examination, measuring distal motor latency and amplitude at 1, 2, 3, and 4 months postrepair. There was no difference in any of the groups in distal motor latency. The amplitude rose incrementally in all groups, and the fetal group had significantly higher amplitudes (p < 0.02) at 1, 2, 3, and 4 months in comparison with the adult group. There was no statistically significant difference between fetal and neonatal nerve repairs at any of the time periods. At the completion of the study, the nerve repair sites were harvested for histologic estimation of mean myelinated fiber density and fiber diameter distribution distal and proximal to the repair site. A greater percentage of myelinated axons crossed the repair site in the fetal group (83 percent) in comparison with the adult group (63 percent) (p < 0.03). Our study also demonstrated significant increases in the number of larger myelinated fibers crossing the repair site in comparison with the neonatal and adult groups (p < 0.04). This study found that fetal nerve healing following surgical repair is superior to that found in adult animals and results in a higher number of larger myelinated fibers crossing the repair site in comparison with adult and neonatal repairs.     

Pluripotential rabbit embryonic stem (ES) cells are capable of forming overt coat color chimeras following injection into blastocysts

The isolation of pluripotent embryonic stem (ES) cell lines from preimplantation rabbit embryos and their in vitro properties have been previously described. In the present investigation, these ES cell lines were further characterized and their capacity to contribute to formation of adult, fertile animals upon injection into recipient New Zealand White blastocysts demonstrated. The efficiency of chimera formation was low (5% of live born), but the degree of chimerism, as assessed by coat color contribution from the Dutch belted strain, was high (10–50%). Thus a significant step is taken toward the development of gene-targeting technology in the rabbit, an animal whose physiology and size lend itself to unique applications in biomedical research. © 1996 Wiley-Liss, Inc.     

Longitudinal roentgencephalometric study of the growth of the New Zealand white rabbit: cumulative and biweekly incremental growth rates for skull and mandible

A longitudinal roentgencephalometric study of the New Zealand white rabbit has documented postnatal skull and mandible growth from 2 to 34 weeks of age. Dorsoventral and lateral radiographs were performed using a specially constructed restrainer that allowed for standardized films and did not require the use of anesthesia. Assessments from 17 male and 12 female rabbits at biweekly intervals documented cumulative growth as well as biweekly incremental growth. Indices reported here include skull length, interzygomatic width, intercondylar width, and mandibular length. Mean skull length at 2 weeks was 54% of that at 34 weeks, and by 16 weeks 91% of adult skull length was achieved. Mean interzygomatic width at 2 weeks was 60% of that at 34 weeks, and by 16 weeks 91% of adult male and 94% of adult female widths were achieved. Mean mandibular length at 2 weeks was 47% of that at 34 weeks, and by age 16 weeks 90% of adult length was achieved. Mean intercondylar width at 2 weeks was 57% of that at 34 weeks, and by 16 weeks 89% of adult male and 93% of adult female widths were achieved. Biweekly increments decreased continually from 2 weeks of age on for all indices.     

Serologic evaluation of New Zealand sea lions for exposure to Brucella and Leptospira spp

A serologic survey of anti-Brucella and antileptospiral antibodies was conducted on 147 adult, female New Zealand sea lions (Phocarctos hookeri). Most sea lions (n=138) were sampled at Sandy Bay, Enderby Island, Auckland Islands (50°30'S, 166°17'E), January 2000-March 2005. Nine were sampled at Otago, New Zealand (46°0'S, 170°40'E); four in April 2008 and five in March 2009. Serum from one of the Enderby Island females was weakly positive for antibodies to Brucella abortus using the competitive enzyme-linked immunosorbent assay, and one female had a low titer for Leptospira interrogans serovar pomona using the microscope agglutination test. All serum samples from Otago animals were negative. Brucellosis and leptospirosis are therefore considered unlikely to play a major role in population dynamics of these populations, and the low antibody prevalence of these agents suggests that they are an unlikely source of infection for humans, wildlife, or domestic species on mainland New Zealand.     

Degeneration-regeneration as a mechanism contributing to the fast to slow conversion of chronically stimulated fast-twitch rabbit muscle

Summary Extensor digitorum longus muscles of male adult White New Zealand rabbits were indirectly stimulated at 10 Hz for 12 h daily for periods ranging up to 28 days. After four weeks the stimulated muscles showed a nearly uniform profile of high succinate dehydrogenase activity and, when incubated after acid preincubation for myofibrillar adenosine triphosphatase, displayed more dark- and intermediate-staining fibers than their contralateral counterparts. Muscles stimulated from between 6 to 21 days revealed degenerative foci and phagocytosis of degenerated fibers. These fibers were mostly of the fast-twitch, glycolytic type. Small myofibers, which often contained central nuclei, and structures identified as myoblasts or myotubes, reacted with a monoclonal antibody prepared against embryonic myosin heavy chains. The data suggest that under the employed conditions the fast to slow conversion of chronically stimulated fast-twitch rabbit muscle is not exclusively caused by adult fiber transformation, but results in part from the substitution of fast-twitch glycolytic fibers with newly formed fibers that have a high oxidative profile.     

A novel locus regulates both retroviral glycoprotein 70 and anti-glycoprotein 70 antibody production in New Zealand mice when crossed with BALB/c

Lupus-prone New Zealand Black and New Zealand White mice produce high serum levels of the endogenous retroviral envelope protein gp70 and develop an Ab response to this autoantigen as part of their autoimmune disease. Linkage analysis of two crosses involving New Zealand and BALB/c mice mapped these traits to a group of overlapping loci, including a novel locus on proximal chromosome 12. This locus was linked with serum gp70 and the autoimmune response against it. The linkage of serum gp70 levels to a previously described locus on distal chromosome 4 was also confirmed. Sequence analysis of a candidate gene on distal chromosome 4, Fv1, provided support that this gene may be associated with the control of serum gp70 levels in both New Zealand Black and New Zealand White mice. Linkage data and statistical analysis confirmed a close correlation between gp70 Ag and anti-gp70 Ab levels, and together gave support to the concept that a threshold level of gp70 is required for the production of anti-gp70 Abs. Serum levels of anti-gp70 Abs were closely correlated with the presence of renal disease, more so than anti-dsDNA Abs. Understanding the genetic basis of this complex autoantigen-autoantibody system will provide insight into the pathogenesis of lupus in mice, which may have implications for human disease.     

Endometrial venous aneurysms in three New Zealand white rabbits.

Hematuria in rabbits has been associated with uterine adenocarcinoma, uterine polyps, renal infarction, urolithiasis, cystitis, bladder polyps, and pyelonephritis. Three adult female New Zealand White rabbits (Oryctolagus cuniculus) developed apparent hematuria, as suggested by blood in their excreta pans. They had been immunized with antigen-adjuvant emulsions, but had uneventful clinical histories. Physical examination disclosed no abnormalities, and laboratory tests, including hematology, serum chemistries, urinalyses, urine cultures, ultrasonography, and intravenous pyelography disclosed mild anemia, hematuria, and proteinuria in two of the rabbits. Antibiotic therapy failed to alleviate clinical signs. Two rabbits were euthanized because of persistent urogenital bleeding and the third rabbit underwent exploratory laparotomy and ovariohysterectomy. Multiple endometrial venous aneurysms were present in the uteri of all rabbits and urogenital bleeding was attributed to episodic bleeding from these lesions. Varices and aneurysms of uterine subserosal and myometrial venous plexuses, but not of endometrial vessels in women have been reported. To our knowledge, endometrial venous aneurysms have not been reported in animals previously. Our findings indicate that the differential diagnoses for sporadic apparent hematuria in female rabbits should include endometrial aneurysms.     

Glycerol incorporation into brain lipids in rat pups born to ethanol-intoxicated dams

The incorporation of labeled glycerol into glycerolipid of rat brain was influenced by the age of the animal (2-month-oldvs. newborn); indeed, 12 min after the administration, diglyceride was the most heavily labeled glycerolipid in the newborn brain, whereas the labeling of glycerophospholipid was highest in the adult. Various amounts of ethanol (0% to 36% of total energy intake) were administered to pregnant female rats, and the brains of their pups were examined for the ability to incorporate labeled glycerol into glycerolipid. The radioactivity incorporated into lipid diminished with increasing the amounts of alcohol consumed. The labeling pattern of lipid classes was also influenced; indeed, the radioactivity of diglyceride decreased markedly, whereas that of triglyceride and glycerophospholipid was affected to a lower degree. The distribution of radioactivity among different phospholipids also varied with age; on a percent basis, phosphatidylcholine was labeled less and phosphatidylinositol was labeled more in the newborn than in the adult. Ethanol influenced the pattern of glycerophospholipid labeling, increasing the radioactivity of phosphatidylserine and decreasing that of phosphatidylinositol.     

Molecular characterization and expression analysis of fat mass and obesity-associated gene in rabbit

Fat mass and obesity-associated (FTO) gene codes for a nuclear protein of the AlkB related nonhaem iron and 2-oxoglutarate-dependent oxygenase superfamily, and is involved in animal fat deposition and human obesity. In this work, the molecular characterization and expression features of rabbit (Oryctolagus cuniculus) FTO cDNA were analysed. The rabbit FTO cDNA with a size of 2158 bp was cloned, including 1515 bp of the open reading frame that encoded a basic protein of 504 amino acids. Homologous comparison indicated that the rabbit FTO shared 36.36–91.88% identity with those from other species and phylogenetic analysis showed that the rabbit FTO is closely related to human, but more distantly related to zebrafish. The New Zealand rabbit FTO mRNA was detected in all tissues examined, with the highest levels found in the spleen and the lowest found in the kidney. However, no significant differences were seen in cerebellum, corpora quadrigemina, medulla oblongata and cerebral cortex of commercial adult rabbits. Moreover, mRNA levels of FTO in liver tissues were significantly increased in lactating New Zealand rabbits compared with 70-day-old, 90-day-old and gestating rabbits (P?<?0.05). In contrast, FTO mRNA levels were significantly lower in longissimus dorsi muscle of 90-day-old New Zealand rabbits than in 70-day-old rabbits (P?<?0.05). However, the expression levels of FTO in mammary gland and ovary of gestating and lactating rabbits were not significantly different (P?>?0.05).     

The development,inhibition and disinhibition of pup-cannibalism in the Mongolian gerbil

The responses of juvenile and adult gerbils towards newborn test pups were investigated. Young animals of both sexes are less likely to attack the test pup than are older animals. Mature females are more likely to attempt to cannibalize pups than are mature males. Attempted cannibalism by adult males is inhibited when their mate becomes pregnant. If the pregnant female is removed from the cage for one to three days, however, attempted cannibalism is disinhibited. On the other hand, males which have reared a previous litter will not harm test pups when the female is removed. Experience of a pregnant female and of young pups during the pre-weaning stage does not influence the incidence of attempted cannibalism in adulthood. These data suggest that gerbils take full advantage of changing social conditions.     

Ultrasound-guided blood sampling of rabbit fetuses.

A rabbit animal model for hemolytic disease of the newborn has been previously described. However, evaluating the effects of this disease was limited to histologic and hematologic examinations of liveborn kitlings. To assess the feasibility of in utero blood sampling, we performed ultrasound-guided cardiac sampling of 50 fetuses in 16 New Zealand White does on days 26 and 27 of gestation. The overall rate of successful sampling was 80%. The procedure-related mortality declined to 35% by the third phase of the study. The mean (+/- SD) hematocrit (%) and reticulocyte values (#/100 RBCs) on day 26 were 26.3 +/- 3.3 and 35.6 +/- 5.1, respectively; values on day 27 were 31.3 +/- 4.9 and 27.5 +/- 7.6. The results of this study suggest that hematologic data can be obtained from rabbit fetuses in the majority of cases with only moderate fetal loss.     

First observation of the courtship behaviour of the giant devil ray Mobula mobular (Myliobatiformes: Mobulidae)

Courtship behaviour of the giant devil ray Mobula mobular is described from northern New Zealand, temperate southwest Pacific Ocean, for the first time. A mating train consisting of a full-term pregnant female and up to four males was observed over a period of 147 minutes. Their behaviour was similar to courtship behaviour observed in other large mobulids. Biting of the female was not observed, possibly due to the female’s use of the surface to prevent males positioning themselves above her. However, the lead male pressed the female’s abdomen and underside each time the female reached or stopped at the surface. The occurrence of pregnant females and mating behaviour off northern North Island confirms breeding occurs in New Zealand waters.     

Progesterone receptor mRNA expression and distribution in the female rabbit brain

Progesterone regulates diverse functions in the rabbit brain through the interaction with its nuclear receptor (PR). Although PR protein has been detected in some regions of the rabbit forebrain, PR mRNA expression and distribution in the rabbit brain are unknown. Hence, we investigated these issues by in situ hybridization. New Zealand adult female rabbits were ovariectomized and treated with vehicle or estradiol (5 μg/(kg day)) for 3 days. The results show an extended distribution of PR mRNA expression in the rabbit brain. The highest expression was detected in preoptic area and hypothalamic anterior nuclei such as paraventricular, periventricular and arcuate nuclei. A high expression was also detected in thalamic and telencephalic areas, including hippocampus and cerebral cortex. Estradiol treatment induced an increase in PR mRNA expression in many brain areas, particularly in the hippocampus and the hypothalamic and preoptic area regions. The wide distribution of PR mRNA in the rabbit brain suggests that progesterone through PR activation is involved in several functions apart from reproductive behavior in rabbits, and that PR expression is up-regulated by estradiol in the rabbit brain.     

Abdominal pregnancies in farm rabbits

Abdominal pregnancy is defined as the implantation and development of a fertilized ovum or a embryo in the peritoneal cavity. Although this has been reported in several species, it is considered as a low incidence process. It is classified as a primary abdominal pregnancy, if there is no evidence of uterine rupture, with presumed regurgitation of early embryos from the uterine tube and as a secondary abdominal pregnancy, when there is evidence of uterine rupture. During a necropsy study of 550 adult fertile female New Zealand white rabbits (Oryctolagus cuniculus) from two rabbit farms in Valencia (Spain), the main causes of elimination were studied. Twenty-eight abdominal pregnancies were diagnosed. Seven animals showed no lesions in their reproductive tract. The remaining twenty one animals showed acute or chronic lesions in the reproductive tract. The classification as a primary or secondary condition is discussed. It may be concluded therefore that extrauterine pregnancies would not be such an unusual finding in rabbits, and that this premise should be considered in the diagnostic approach when assessing rabbit doe pathology. New husbandry systems in rabbits such as artificial insemination are factors to be considered.     

Teratologic evaluation of synthetic delta 9-tetrahydrocannabinol in rabbits.

Synthetic delta 9-tetrahydrocannabinol (THC) was dissolved in undiluted propylene glycol and administered in daily subcutaneous doses of 15.0, 30.0 or 60.0 mg/kg to pregnant New Zealand white rabbits on days 7--19 of gestation. Maternal food consumption and weight gain were markedly reduced at all dose levels. Embryotoxicity and embryocidal effects were observed in the form of reduced litter weight and number of viable fetuses, respectively, in offspring from pregnant mothers treated with THC. However, on the basis of extensive external, visceral and skeletal examination of all fetuses it may be concluded that THC is not teratogenic in the New Zealand white strain rabbit following subcutaneous administration of doses as high as 60.0 mg/kg/day during the critical period of organogenesis (days 7--19 of gestation). On the other hand, an oral dose of thalidomide (200.0 mg/kg/day), the positive control used in this study, was both embryocidal and teratogenic.     

Molecular profiling and identification of methanogenic archaeal species from rabbit caecum

During a comparison of 16S rDNA PCR-denaturant gradient gel electrophoresis (DGGE) profiles of methanogenic archaea from rumen fluid, rabbit caecum and pig feces, a unique band common to all rabbit caecum samples was observed. DGGE profiling also showed that the methanogen community from the New Zealand White adult rabbits is different and less complex than the methanogen communities from the rumen and pig feces. Small subunit ribosomal gene sequences of methanogenic archaea were subsequently retrieved from the constructed rabbit caecum 16S rDNA gene library. Results of the phylogenetic analysis indicated that rabbit caecum is inhabited by members of the genus Methanobrevibacter and is possibly one-species dominated, because all the retrieved sequences exhibited similarity values of 99% or higher. This species may well be a novel species of the genus Methanobrevibacter. It belongs to a distinct phylogenetic group containing Methanobrevibacter woesei, Methanobrevibacter thaueri and Methanobrevibacter gottschalkii strains isolated from animal feces, and Methanobrevibacter smithii from the predominating methanogen population of the human large bowel.     

Species and tissue distribution of the 4S carcinogen binding protein and its possible role in cytochrome P-450 induction

A carcinogen binding protein (CBP) that is implicated in controlling the expression of rat cytochrome P-450c which is closely associated with aryl hydrocarbon hydroxylase (AHH) was examined in hepatic and extrahepatic tissues of the neonatal and adult New Zealand White (NZW) rabbits, the hepatic tissue of the BALB/cJ and DBA/2J mice, Brown Norway rat, Golden Syrian hamster and Hartley guinea pig. These animals and tissues were examined in order to determine whether there was a correlation of CBP levels and the reported presence or absence of inducibility of AHH in these tissues. The CBP was found in hepatic and extrahepatic tissue of the NZW rabbit and the hepatic tissues of all animals except the Hartley guinea pig. The Hartley guinea pig may provide a useful animal with which to further examine the role of CBP in cytochrome induction. Since the CBP is not a tissue specific protein and because it is found in both neonatal and adult NZW rabbit tissue, the data suggests that the CBP is not the limiting factor in the tissue specific induction of cytochromes nor in developmentally controlled induction of cytochromes previously reported in the rabbit.