Mouse models of IgG- and IgM-mediated hemolysis

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 3099-3107 ◽  
Author(s):  
David A. Schirmer ◽  
Shuh-Chyung Song ◽  
Jeffrey P. Baliff ◽  
Stephanie O. Harbers ◽  
Raphael A. Clynes ◽  
...  

Abstract Well-characterized mouse models of alloimmune antibody-mediated hemolysis would provide a valuable approach for gaining greater insight into the pathophysiology of hemolytic transfusion reactions. To this end, mouse red blood cells (mRBCs) from human glycophorin A transgenic (hGPA-Tg) donor mice were transfused into non-Tg recipients that had been passively immunized with IgG or IgM hGPA-specific monoclonal antibodies (mAbs). In this novel murine “blood group system,” mRBCs from hGPA-Tg mice are “antigen positive” and mRBCs from non-Tg mice are “antigen negative.” Passive immunization of non-Tg mice with the IgG1 10F7 and IgG3 NaM10-2H12 anti-hGPA mAbs each induced rapid clearance of incompatible transfused hGPA-Tg-mRBCs in a dose-response manner. Using various knockout mice as transfusion recipients, both the complement system and activating Fcγ receptors were found to be important in the clearance of incompatible mRBCs by each of these IgG mAbs. In addition, the IgM E4 anti-hGPA mAb induced complement-dependent intravascular hemolysis of transfused incompatible hGPA-Tg-mRBCs accompanied by gross hemoglobinuria. These initial studies validate the relevance of these new mouse models for addressing important questions in the field of transfusion medicine.

Author(s):  
OJS Admin

Blood groups ABO and Rhesus, constituting the most principal blood group system, are of key signicance for clinical and transfusion practices and are moreover, thought to be associated with disease susceptibility.


Antibody Fc ◽  
2014 ◽  
pp. 49-74 ◽  
Author(s):  
Margaret A. Lindorfer ◽  
Jörg Köhl ◽  
Ronald P. Taylor

Author(s):  
Mikhail V. Pletnikov ◽  
Christopher A. Ross

Despite the recent advances in research into schizophrenia and bipolar disorder, the neurobiology of these maladies remains poorly understood. Animal models can be instrumental in elucidating the underlying mechanisms of neuropsychiatric disorders. Early animal models of schizophrenia and bipolar disorder used lesion methods, pharmacologic challenges or environmental interventions to mimic pathogenic features of the diseases. The recent progress in genetics has stimulated the development of etiological models that have begun to provide insight into pathogenesis. In this review, we evaluate the strengths and weaknesses of the existing genetic mouse models of schizophrenia and discuss potential developments for the future.


BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Sandra Louzada ◽  
Walid Algady ◽  
Eleanor Weyell ◽  
Luciana W. Zuccherato ◽  
Paulina Brajer ◽  
...  

2008 ◽  
Vol 42 (1) ◽  
pp. 11-17 ◽  
Author(s):  
S Kerkhofs ◽  
S Denayer ◽  
A Haelens ◽  
F Claessens

Androgens play an important role in male reproductive development and function. These steroid hormones mediate their actions by binding to the androgen receptor (AR). Diseases such as androgen insensitivity syndrome, prostate cancer, Kennedy's disease, and infertility can be caused by mutations in the AR. To get a better insight into the molecular working mechanisms of the AR, several knockout and knock-in mouse models have been developed. These models are reviewed here and are compared with human diseases.


2009 ◽  
Vol 77 (12) ◽  
pp. 5291-5299 ◽  
Author(s):  
Francisco A. Uzal ◽  
Juliann Saputo ◽  
Sameera Sayeed ◽  
Jorge E. Vidal ◽  
Derek J. Fisher ◽  
...  

ABSTRACT Clostridium perfringens type C isolates cause enterotoxemias and enteritis in humans and livestock. While the major disease signs and lesions of type C disease are usually attributed to beta toxin (CPB), these bacteria typically produce several different lethal toxins. Since understanding of disease pathogenesis and development of improved vaccines is hindered by the lack of small animal models mimicking the lethality caused by type C isolates, in this study we developed two mouse models of C. perfringens type C-induced lethality. When inoculated into BALB/c mice by intragastric gavage, 7 of 14 type C isolates were lethal, whereas when inoculated intraduodenally, these strains were all lethal in these mice. Clinical signs in intragastrically and intraduodenally challenged mice were similar and included respiratory distress, abdominal distension, and neurological alterations. At necropsy, the small, and occasionally the large, intestine was dilated and gas filled in most mice developing a clinical response. Histological changes in the gut were relatively mild, consisting of attenuation of the mucosa with villus blunting. Inactivation of the CPB-encoding gene rendered the highly virulent type C strain CN3685 avirulent in the intragastric model and nearly nonlethal in the intraduodenal model. In contrast, inactivation of the genes encoding alpha toxin and perfringolysin O only slightly decreased the lethality of CN3685. Mice could be protected against lethality by intravenous passive immunization with a CPB antibody prior to intragastric challenge. This study proves that CPB is a major contributor to the systemic effects of type C infections and provides new mouse models for investigating the pathogenesis of type C-induced lethality.


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