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Strain-dependent differences in bone development, myeloid hyperplasia, morbidity and mortality in ptpn2-deficient mice.

ABSTRACT: Single nucleotide polymorphisms in the gene encoding the protein tyrosine phosphatase TCPTP (encoded by PTPN2) have been linked with the development of autoimmunity. Here we have used Cre/LoxP recombination to generate Ptpn2(ex2-/ex2-) mice with a global deficiency in TCPTP on a C57BL/6 background and compared the phenotype of these mice to Ptpn2(-/-) mice (BALB/c-129SJ) generated previously by homologous recombination and backcrossed onto the BALB/c background. Ptpn2(ex2-/ex2-) mice exhibited growth retardation and a median survival of 32 days, as compared to 21 days for Ptpn2(-/-) (BALB/c) mice, but the overt signs of morbidity (hunched posture, piloerection, decreased mobility and diarrhoea) evident in Ptpn2(-/-) (BALB/c) mice were not detected in Ptpn2(ex2-/ex2-) mice. At 14 days of age, bone development was delayed in Ptpn2(-/-) (BALB/c) mice. This was associated with increased trabecular bone mass and decreased bone remodeling, a phenotype that was not evident in Ptpn2(ex2-/ex2-) mice. Ptpn2(ex2-/ex2-) mice had defects in erythropoiesis and B cell development as evident in Ptpn2(-/-) (BALB/c) mice, but not splenomegaly and did not exhibit an accumulation of myeloid cells in the spleen as seen in Ptpn2(-/-) (BALB/c) mice. Moreover, thymic atrophy, another feature of Ptpn2(-/-) (BALB/c) mice, was delayed in Ptpn2(ex2-/ex2-) mice and preceded by an increase in thymocyte positive selection and a concomitant increase in lymph node T cells. Backcrossing Ptpn2(-/-) (BALB/c) mice onto the C57BL/6 background largely recapitulated the phenotype of Ptpn2(ex2-/ex2-) mice. Taken together these results reaffirm TCPTP's important role in lymphocyte development and indicate that the effects on morbidity, mortality, bone development and the myeloid compartment are strain-dependent.

SUBMITTER: Wiede F

PROVIDER: S-EPMC3348136 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Strain-dependent differences in bone development, myeloid hyperplasia, morbidity and mortality in ptpn2-deficient mice.

Wiede Florian F Chew Sock Hui SH van Vliet Catherine C Poulton Ingrid J IJ Kyparissoudis Konstantinos K Sasmono Tedjo T Loh Kim K Tremblay Michel L ML Godfrey Dale I DI Sims Natalie A NA Tiganis Tony T

PloS one 20120508 5

Single nucleotide polymorphisms in the gene encoding the protein tyrosine phosphatase TCPTP (encoded by PTPN2) have been linked with the development of autoimmunity. Here we have used Cre/LoxP recombination to generate Ptpn2(ex2-/ex2-) mice with a global deficiency in TCPTP on a C57BL/6 background and compared the phenotype of these mice to Ptpn2(-/-) mice (BALB/c-129SJ) generated previously by homologous recombination and backcrossed onto the BALB/c background. Ptpn2(ex2-/ex2-) mice exhibited g ...[more]

PMID: 22590589

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Project description:BackgroundCoronary artery bypass grafting (CABG) is associated with both cardiovascular disease (CVD) and non-CVD traits. In addition, women's prognosis after coronary events and revascularizations is worse than in men. As the course of CVD in women differs from that of men, we performed a phenome-wide analysis on the sex differences in CABG -related morbidity and mortality.Materials and methodsWe performed an untargeted analysis on the sex differences in predictors and outcomes of CABG. We studied a sample of 176,680 FinnGen participants, including 5,950 individuals who underwent CABG (4,988 men and 962 women) and were followed between 1998 and 2019. Over 1,100 different traits were analyzed for both sexes and the results were adjusted with age, smoking status and BMI. Cox proportional hazards models with sex-trait interactions were used to estimate the associations between (1) traits and incident CABG; and (2) CABG and incident traits.ResultsIn women, CABG was more strongly related to greater increases in risk of diseases such as hypertension, Alzheimer's, aortic aneurysms, gout, and chronic kidney disease compared to risk increases observed in men (all interaction p-values < 0.03). After CABG, men had 2.5-fold (p = 3.1E-15) and women 6.3-fold (p = 9.4E-08) greater risk of cardiac death compared to same-sex individuals who did not undergo CABG (p for interaction 8.2E-4). Moreover, the risk of death in women remained higher even 12 years after CABG, whereas the long-term risk of death in men was not increased, compared to same-sex individuals who did not undergo CABG.ConclusionThe adverse outcomes after CABG, both quantity and quality, also appear to differ between men and women. In women, CABG is related to greater long-term increases in risk of cardiac death and several other disease states than in men. Consideration should therefore be given to whether women receive adequate long-term post-operative therapy and follow-up as CABG is not associated with equally improved cardiovascular disease prognosis in women than in men.

Dataset Information

Strain-dependent differences in bone development, myeloid hyperplasia, morbidity and mortality in ptpn2-deficient mice.

Publications

Strain-dependent differences in bone development, myeloid hyperplasia, morbidity and mortality in ptpn2-deficient mice.

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