Spontaneous diabetes mellitus in the New Zealand white rabbit

Conaway, H. Herschel; Brown, C. J.; Sanders, Louis L.; Cernosek, Stanley F.; Farris, Harold E.; Roth, Sanford I.

doi:10.1093/oxfordjournals.jhered.a109343

Cited by 17 publications

(4 citation statements)

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“…The heterozygous male mice develop hyperglycemia and hypoinsulinemia at 4 weeks postnatal and progress to develop the well-known signs of diabetes. They exhibit signs similar to early pathophysiological changes of diabetic complications, [5][6][7][8][9][10][11] but fail to develop any of the advanced stages of these complications. Analysis of retinae of Ins2…”

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confidence: 99%

Characterization of a Mouse Model of Hyperglycemia and Retinal Neovascularization

Rakoczy

Rahman

Binz

et al. 2010

The American Journal of Pathology

102

147

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One of the limitations of research into diabetic retinopathy is the lack of suitable animal models. To study how the two important factors-hyperglycemia and vascular endothelial growth factor-interact in diabetic retinopathy, the Akimba mouse (Ins2 ). C57Bl/6 and the parental and Akimba mouse lines were characterized by biometric measurements, histology, immunohistochemistry, and Spectralis Heidelberg retinal angiography and optical coherence tomography. The Akimba line not only retained the characteristics of the parental strains, such as developing hyperglycemia and retinal neovascularization, but developed higher blood glucose levels at a younger age and had worse kidney-body weight ratios than the Akita line. With aging, the Akimba line demonstrated enhanced photoreceptor cell loss, thinning of the retina, and more severe retinal vascular pathology, including more severe capillary nonperfusion, vessel constriction, beading, neovascularization, fibroses, and edema, compared with the Kimba line. The vascular changes were associated with major histocompatibility complex class II ؉ cellular staining throughout the retina. Together, these observations suggest that hyperglycemia resulted in higher prevalences of edema and exacerbated the vascular endothelial growth factordriven neovascular and retinal changes in the Akimba line. Thus, the Akimba line could become a useful model for studying the interplay between hyperglycemia and vascular endothelial growth factor and for testing treatment strategies for potentially blinding complications, such as edema.

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mentioning

confidence: 99%

Characterization of a Mouse Model of Hyperglycemia and Retinal Neovascularization

Rakoczy

Rahman

Binz

et al. 2010

The American Journal of Pathology

102

147

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“…The results support the use of rabbits as an animal model to study the involvement of risk factors related to the genesis of AD‐like cognitive deficits and alterations of intrinsic connectivity. The human‐like amino acid sequence for rabbit amyloid; structural similarity of rabbit and human tau; human‐like lipid physiology; an APOE sequence that is 80% homologous to the APOE ε3 isoform, 40 the most common isoform in humans; and a spontaneous ability for rabbits to develop Type 2 diabetes, 41 make the rabbit a good model to study the genesis of AD and the effects of potential therapeutics. The rabbit provides an additional tool alongside murine genetic models to investigate more thoroughly the underlying mechanisms and causes of AD.…”

Section: Discussionmentioning

confidence: 99%

Diet‐induced Alzheimer's‐like syndrome in the rabbit

Weiss

Bertolino

Procissi

et al. 2022

A&D Transl Res & Clin Interv

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Introduction:Although mouse models of Alzheimer's disease (AD) have increased our understanding of the molecular basis of the disease, none of those models represent late-onset Alzheimer's Disease which accounts for >90% of AD cases, and no therapeutics developed in the mouse (with the possible exceptions of aduhelm/aducanumab and gantenerumab) have succeeded in preventing or reversing the disease. This technology has allowed much progress in understanding the molecular basis of AD. To further enhance our understanding, we used wild-type rabbit (with a nearly identical amino acid sequence for amyloid as in humans) to model LOAD by stressing risk factors including age, hypercholesterolemia, and elevated blood glucose levels (BGLs), upon an ε3-like isoform of apolipoprotein. We report a combined behavioral, imaging, and metabolic study using rabbit as a non-transgenic model to examine effects of AD-related risk factors on cognition, intrinsic functional connectivity, and magnetic resonance-based biomarkers of neuropathology.Methods: Aging rabbits were fed a diet enriched with either 2% cholesterol or 10% fat/30% fructose. Monthly tests of novel object recognition (NOR) and object location memory (OLM) were administered to track cognitive impairment. Trace eyeblink conditioning (EBC) was administered as a final test of cognitive impairment. Magnetic resonance imaging (MRI) was used to obtain resting state connectivity and quantitative parametric data (R 2 *).Results: Experimental diets induced hypercholesterolemia or elevated BGL. Both experimental diets induced statistically significant impairment of OLM (but not NOR) and altered intrinsic functional connectivity. EBC was more impaired by fat/fructose diet than by cholesterol. Whole brain and regional R 2 * MRI values were elevated in both experimental diet groups relative to rabbits on the control diet.Discussion: We propose that mechanisms underlying LOAD can be assessed by stressing risk factors for inducing AD and that dietary manipulations can be used to assess etiological differences in the pathologies and effectiveness of potential therapeuticsThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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“…Its substrains, such as Komeda diabetes-prone rats and LEW.1AR1/Ztmiddm are also raised from Lewis rats by a spontaneous mutation [98][99][100]. However, some animal models such as Chinese hamsters and Keeshond dogs [101], as well as New Zealand white rabbits [102], are less frequently used in Type 1 diabetic research.…”

Section: Genetic Modelsmentioning

confidence: 99%

Animal Models in Diabetic Research—History, Presence, and Future Perspectives

Pandey,

Chmelir,

Chottova Dvorakova

2023

Biomedicines

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Diabetes mellitus (DM) is a very serious disease, the incidence of which has been increasing worldwide. The beginning of diabetic research can be traced back to the 17th century. Since then, animals have been experimented on for diabetic research. However, the greatest development of diabetes research occurred in the second half of the last century, along with the development of laboratory techniques. Information obtained by monitoring patients and animal models led to the finding that there are several types of DM that differ significantly from each other in the causes of the onset and course of the disease. Through different types of animal models, researchers have studied the pathophysiology of all types of diabetic conditions and discovered suitable methods for therapy. Interestingly, despite the unquestionable success in understanding DM through animal models, we did not fully succeed in transferring the data obtained from animal models to human clinical research. On the contrary, we have observed that the chances of drug failure in human clinical trials are very high. In this review, we will summarize the history and presence of animal models in the research of DM over the last hundred years. Furthermore, we have summarized the new methodological approaches, such as “organ-on-chip,” that have the potential to screen the newly discovered drugs for human clinical trials and advance the level of knowledge about diabetes, as well as its therapy, towards a personalized approach.

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Spontaneous diabetes mellitus in the New Zealand white rabbit

Cited by 17 publications

References 0 publications

Characterization of a Mouse Model of Hyperglycemia and Retinal Neovascularization

Characterization of a Mouse Model of Hyperglycemia and Retinal Neovascularization

Diet‐induced Alzheimer's‐like syndrome in the rabbit

Animal Models in Diabetic Research—History, Presence, and Future Perspectives

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