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Unexpected mortality occurred in a group of 12 NOD.Cg-NOD.Cg- Prkdc scid Il2rg tm1Wjl /SzJ (NSG) and 12 NOD.Cg- Rag1 tm1Mom Il2rg tm1Wjl /SzJ (NRG) immunodeficient mice. At 10 d after routine bone marrow-liver-thymus humanization surgery, 9 mice were found dead without observation of initiating clinical signs; 1 d later (day 11), 3 additional mice showed signs of morbidity, including severe hunching, lateral recumbency, slow movement, shallow respiration, and decreased response to external stimulus. All remaining mice rapidly decompensated and were found dead or were euthanized within 4 d after the first death. Histopathology revealed severe ascending pyelonephritis with numerous yeast. Cultures in some mice were positive for Enterococcus faecalis or Staphylococcus xylosus , 2 bacteria considered commensals in rodents. In addition, Candida albicans was cultured from some animals. Further investigation revealed that a restraining device used for tail vein injections was the likely fomite harboring Candida organisms. These findings indicate that ascending pyelonephritis, with Candida as the etiologic agent, can cause significant mortality in NSG and NRG immunodeficient mice.

Using the intrinsic optical properties of collagen and elastin, two-photon microscopy was applied to evaluate the three-dimensional (3D) macromolecular structural development of the mouse thoracic aorta from birth to 60 days old. Baseline development was established in the Scavenger Receptor Class B Type I-Deficient, Hypomorphic Apolipoprotein ER61 (SR-BI KO/ApoeR61(h/h)) mouse in preparation for modeling atherosclerosis. Precise dissection enabled direct observation of the artery wall in situ. En-face, optical sectioning of the aorta provided a novel assessment of the macromolecular structural development. During aortic development, the undulating lamellar elastin layers compressed consistent with the increases in mean aortic pressure with age. In parallel, a net increase in overall wall thickness (p<0.05, in day 60 compared with day 1 mice) occurred with age whereas the ratio of the tunicas adventitia and media to full aortic thickness remained nearly constant across age groups (~1:2.6, respectively). Histochemical analyses by brightfield microscopy and ultrastructure validated structural proteins and lipid deposition findings derived from two-photon microscopy. Development was associated with decreased decorin but not biglycan proteoglycan expression. This non-destructive 3D in situ approach revealed the aortic wall microstructure development. Coupling this approach with the intrinsic optical properties of the macromolecules may provide unique vascular wall 3D structure in many pathological conditions, including aortic atherosclerosis, dissections and aneurysms., (© The Author(s) 2014.)