Clinical Chemistry of the Laboratory Mouse

Quimby, Fred W.; Luong, Richard

doi:10.1016/b978-012369454-6/50060-1

Cited by 32 publications

(22 citation statements)

References 246 publications

(227 reference statements)

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“…This finding correlates with the increased incidence of EHEC-associated HUS in children compared to adults (2,18). We also showed that while (as previously described for mice [37]) BUN is an insensitive marker of renal disease, urine specific gravity is a sensitive indicator of the onset of renal failure and correlates well with histologic evidence of renal disease. This has not been shown previously in a mouse model of EHEC.…”

Section: %)supporting

confidence: 64%

Pathogenesis of Renal Disease Due to Enterohemorrhagic Escherichia coli in Germ-Free Mice

et al. 2008

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Enterohemorrhagic Escherichia coli (EHEC) is a food-borne pathogen that causes hemorrhagic colitis and acute renal failure. We used a germ-free mouse model to investigate the role of host factors, Shiga toxin 2 (Stx2), and bacterial strain in disease due to EHEC. Germ-free male and female Swiss-Webster mice that were 3 days to 12 weeks old were orally inoculated with 1 of 10 EHEC strains or derivatives of two of these strains with Stx2 deleted. All inoculated mice became infected regardless of the inoculum dose. All bacterial strains colonized the intestines, reaching levels of 10 9 to 10 12 CFU/g of feces by 4 days after inoculation. Seven of the 10 wild-type strains caused disease. However, the two Stx2 deletion mutants, unlike the Stx2 ؉ parental strains, did not cause disease. The clinical signs of disease in mice included lethargy, dehydration, polyuria, polydypsia, and death. Postmortem examination of affected mice revealed dehydration and luminal cecal fluid accumulation. Histologic examination revealed close adherence of bacteria to the intestinal epithelium in the ileum and cecum but not in the colon. Other lesions included progressive renal tubular necrosis, glomerular fibrin thrombosis, and red blood cell sludging. The severity of disease varied according to the bacterial strain and age, but not sex, of the host. This study demonstrated that EHEC colonizes germ-free mice in large numbers, adheres to the intestinal epithelium, and causes luminal cecal fluid accumulation and progressive renal failure. The disease in mice was Stx2 and bacterial strain dependent. This animal model should be a useful tool for studying the pathogenesis of renal disease secondary to EHEC infection.Enterohemorrhagic Escherichia coli (EHEC), a food-borne bacterial pathogen of humans, is a normal inhabitant of the ruminant intestine. This organism is most often transmitted to humans in undercooked meat, but it has also caused outbreaks associated with contaminated vegetables (5, 28), fruit juices (6), and drinking water (41). The disease manifestations include watery or bloody diarrhea and can be severe enough to cause hospitalization and even death (18). In addition, some affected children (and rarely adults) develop hemolytic-uremic syndrome (HUS), a rapidly progressive, often fatal form of renal failure that is attributed to expression of Shiga toxins (Stx) by pathogenic bacteria (2, 18). HUS is defined by a triad of symptoms that includes hemolysis, uremia, and thrombocytopenia. It is a rare complication of disease due to EHEC, but its importance is amplified by its severity, tendency to affect young children, and the absence of any specific treatment or preventative measure. Thus, the significance of disease due to EHEC is derived from its food-borne nature and its potentially severe consequences.Both HUS and hemorrhagic colitis caused by EHEC have been attributed to the production of Stx by pathogenic bacteria (2, 50) referred to as Stx-producing E. coli (STEC). The Stxs are macromolecular cytotoxins that are phage encode...

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Section: %)supporting

confidence: 64%

Pathogenesis of Renal Disease Due to Enterohemorrhagic Escherichia coli in Germ-Free Mice

et al. 2008

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“…5E) and total bilirubin (Fig. 5F) levels were increased by 297% and 411%, respectively, over the levels in the blood of the mock-infected controls (71). Meanwhile, the mean levels of ALP and total bilirubin were similar between mice infected with the Y259H and R1182G mutants and mock-infected control mice, while the mean ALT level in samples from mice infected with the R1182G mutant were increased by 363% over that in samples from the mock-infected control mice, which exceeds the physiologically normal ALT level (71) (Fig.…”

Section: Resultsmentioning

confidence: 94%

Rift Valley Fever Virus MP-12 Vaccine Is Fully Attenuated by a Combination of Partial Attenuations in the S, M, and L Segments

Ikegami

Hill

Smith

et al. 2015

J Virol

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Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and characterized by a high rate of abortion in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. RVF is caused by Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), which has a tripartite negative-stranded RNA genome (consisting of the S, M, and L segments). Further spread of RVF into countries where the disease is not endemic may affect the economy and public health, and vaccination is an effective approach to prevent the spread of RVFV. A live-attenuated MP-12 vaccine is one of the best-characterized RVF vaccines for safety and efficacy and is currently conditionally licensed for use for veterinary purposes in the United States. Meanwhile, as of 2015, no other RVF vaccine has been conditionally or fully licensed for use in the United States. The MP-12 strain is derived from wild-type pathogenic strain ZH548, and its genome encodes 23 mutations in the three genome segments. However, the mechanism of MP-12 attenuation remains unknown. We characterized the attenuation of wild-type pathogenic strain ZH501 carrying a mutation(s) of the MP-12 S, M, or L segment in a mouse model. Our results indicated that MP-12 is attenuated by the mutations in the S, M, and L segments, while the mutations in the M and L segments confer stronger attenuation than those in the S segment. We identified a combination of 3 amino acid changes, Y259H (Gn), R1182G (Gc), and R1029K (L), that was sufficient to attenuate ZH501. However, strain MP-12 with reversion mutations at those 3 sites was still highly attenuated. Our results indicate that MP-12 attenuation is supported by a combination of multiple partial attenuation mutations and a single reversion mutation is less likely to cause a reversion to virulence of the MP-12 vaccine. IMPORTANCERift Valley fever (RVF) is a mosquito-transmitted viral disease that is endemic to Africa and that has the potential to spread into other countries. Vaccination is considered an effective way to prevent the disease, and the only available veterinary RVF vaccine in the United States is a live-attenuated MP-12 vaccine, which is conditionally licensed. Strain MP-12 is different from its parental pathogenic RVFV strain, strain ZH548, because of the presence of 23 mutations. This study determined the role of individual mutations in the attenuation of the MP-12 strain. We found that full attenuation of MP-12 occurs by a combination of multiple mutations. Our findings indicate that a single reversion mutation will less likely cause a major reversion to virulence of the MP-12 vaccine.

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“…The present study confirmed that mice were not in a state of inflammation using white blood cell analysis. All white blood cell parameters were within the normal range in the PM24 group, although the lymphocyte counts were at baseline levels (27,28). The parameters were similar to those identified in a previous study (29), which demonstrated that total white blood cell and lymphocyte counts decrease with age, while neutrophil, monocyte and eosinophil counts increase in mice.…”

Section: Discussionmentioning

confidence: 99%

Age-associated alterations in constitutively expressed cyclooxygenase-2 immunoreactivity and protein levels in the hippocampus

Jung

Yoo

Kim

et al. 2017

Molecular Medicine Reports

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Abstract. Cyclooxygenase-2 (COX-2) is a known inducible inflammatory mediator. COX-2 is constitutively expressed in the hippocampus and may regulate synaptic plasticity. The present study investigated the age-associated alterations in white blood cell counts and hippocampal COX-2 expression in healthy mice using immunohistochemical and western blot analyses at 1 month postnatal (PM1), PM3, PM6, PM12 and PM24. White blood cell counts were significantly decreased in the PM24 group when compared with the PM1 group. In addition, lymphocyte counts were decreased in the PM24 group when compared with all other groups. By contrast, monocyte, neutrophil and eosinophil counts were increased in the PM24 group; however, this did not reach statistical significance. COX-2 expression was identified in the granule cells of the dentate gyrus and in the pyramidal cells of the hippocampal CA2/3 region. COX-2 immunoreactivity was maintained until PM18, however, the levels significantly decreased by PM24. These results suggest that, despite alterations in the differential white blood cell counts, the significant decrease in constitutive COX-2 expression in the hippocampus may be associated with degenerative age-associated alterations in synaptic plasticity in the hippocampus.

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Clinical Chemistry of the Laboratory Mouse

Cited by 32 publications

References 246 publications

Pathogenesis of Renal Disease Due to Enterohemorrhagic Escherichia coli in Germ-Free Mice

Pathogenesis of Renal Disease Due to Enterohemorrhagic Escherichia coli in Germ-Free Mice

Rift Valley Fever Virus MP-12 Vaccine Is Fully Attenuated by a Combination of Partial Attenuations in the S, M, and L Segments

Age-associated alterations in constitutively expressed cyclooxygenase-2 immunoreactivity and protein levels in the hippocampus

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