BXSB-type genome causes murine autoimmune glomerulonephritis: pathological correlation between telomeric region of chromosome 1 and Yaa

Abstract

The autoimmune-prone BXSB/MpJ-Yaa mouse is a model of membranous proliferative glomerulonephritis (MPGN). Severe MPGN has been reported only in male BXSB/MpJ-Yaa mice because of the Y-linked autoimmune accelerator (Yaa) locus. However, we show that female BXSB/MpJ mice develop age-related MPGN without Yaa. Female BXSB/MpJ mice clearly developed MPGN characterized by increased mesangial cells, thickening of the glomerular basement membrane (GBM), double contouring and spike formation of GBM with T-cell infiltrations and podocyte injuries corresponding with increased autoantibody production and albuminuria. Analysis of the renal levels of the Fc gamma receptor (Fcgr) and interferon-activated gene 200 (Ifi200) family genes, which are MPGN candidate genes localized to the telomeric region of chromosome 1 (Chr.1), showed that Fcgr2b levels decreased, whereas Fcgr3 and Ifi202b levels increased in female BXSB/MpJ mice compared with healthy C57BL/6 mice. Furthermore, in isolated glomeruli, microarray analysis revealed that Fcgr3, Fcgr4 and Ifi202b expression was higher in male BXSB/MpJ-Yaa mice than in male BXSB/MpJ mice. These findings indicate that the BXSB/MpJ-type genome causes age-related MPGN with significant contribution from the telomeric region of Chr.1, and Yaa enhances the expression of genes localizing to this locus, thereby leading to severe MPGN in male mice.

Comparative analysis of mediastinal fat‐associated lymphoid cluster development and lung cellular infiltration in murine autoimmune disease models and the corresponding normal control strains

“…7 Furthermore, we recently reported that not only male BXSB/MpJ-Yaa mice, but also female BXSB/MpJ mice, clearly exhibit symptoms of age-related autoimmune disease onset, such as increased spleen weights, elevated serum autoantibodies and glomerulonephritis, without the contribution of the Yaa mutation. 44,45 For the BXSB/MpJ strain, age-related autoimmune disease onset was attributed to the expression of immune-associated genes in the telomeric regions of chromosome 1. 45 Therefore, gene mutations as well as genetic backgrounds associated with the immune response may also be important in the development of MFALCs and lung cellular infiltration in murine autoimmune disease models.…”

“…44,45 For the BXSB/MpJ strain, age-related autoimmune disease onset was attributed to the expression of immune-associated genes in the telomeric regions of chromosome 1. 45 Therefore, gene mutations as well as genetic backgrounds associated with the immune response may also be important in the development of MFALCs and lung cellular infiltration in murine autoimmune disease models.…”

Congenic mice demonstrate the presence of QTLs conferring obesity and hypercholesterolemia on chromosome 1 in the TALLYHO mouse

“…Total RNA (2 µg) was reverse-transcribed with SUPERSCRIPT RT using oligo dT as primer to synthesize first-strand cDNA in 20-µl volume according to manufacturer’s instructions (Invitrogen, Waltham, MA). The primers used for the qRT-PCR for the interferon activated gene 202B ( Ifi202b ) gene were synthesized (Sigma) using sequences obtained from the published literature (forward: 5′-GGCAATGTCCAACCGTAACT-3′ and reverse: 5′-TAGGTCCAGGAGAGGCTTGA-3′) (Kimura et al 2014) and the primers for apolipoprotein A135 II ( Apoa2 ) gene were proprietary (PPM05347B, Qiagen). The real-time PCR reaction was carried out in a 25-µl volume in 1x SYBR Green PCR core reagents (Qiagen) containing 1 µl cDNA template diluate (1:5, v/v) and 6 pmol primers using the StepOne™ Real-Time PCR system (Thermo Fisher Scientific).…”

Immune Relevant and Immune Deficient Mice: Options and Opportunities in Translational Research

“…This genetic source of diversity can be ultimately ascribed to a number of possible genetic alterations/variations including polymorphic alleles, unique quantitative trait loci (QTL) intervals, or specific haplotypes. [28][29][30][31][32][33][34][35][36] The influence of the inbred genetic background pervades many if not all the experimental contexts considered in this review.…”

“…111 Spontaneous lupus-like conditions in mice are associated with mutations such as Fas lpr and Yaa and are influenced by genetic background. [28][29][30][31][32][33][34][35][36] Inbred strains that spontaneously develop lupus-like conditions include MRL/MpJ, BXSB/MpJ, NZB, NZW, NZBWF1 (aka NZB/W), NZM2410, and Palmerston North (PN/nBSwUmabJ). 112,63,113,114 MRL/MpJ inbred mice are autoimmune prone and spontaneously develop an autoimmune phenotype as they age.…”