Strain-Dependent Differences in Bone Development, Myeloid Hyperplasia, Morbidity and Mortality in Ptpn2-Deficient Mice

被引：28

作者：

Wiede, Florian ^{[1
]}

Chew, Sock Hui ^{[1
]}

van Vliet, Catherine ^{[1
]}

Poulton, Ingrid J. ^{[2
]}

Kyparissoudis, Konstantinos ^{[3
]}

Sasmono, Tedjo ^{[1
]}

Loh, Kim ^{[1
]}

Tremblay, Michel L. ^{[4
,5
]}

Godfrey, Dale I. ^{[3
]}

Sims, Natalie A. ^{[2
]}

Tiganis, Tony ^{[1
]}

机构：

[1] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia

[2] St Vincents Inst Med Res, Melbourne, Vic, Australia

[3] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia

[4] McGill Univ, McGill Canc Ctr, Montreal, PQ, Canada

[5] McGill Univ, Dept Biochem, Montreal, PQ, Canada

来源：

PLOS ONE | 2012年 / 7卷 / 05期

基金：

英国医学研究理事会;

关键词：

PROTEIN-TYROSINE-PHOSPHATASE; GROWTH-FACTOR RECEPTOR; TC-PTP; NEGATIVE REGULATOR; MARROW MICROENVIRONMENT; EMBRYONIC LETHALITY; SIGNALING PATHWAY; DEFICIENT MICE; EGF RECEPTOR; STEM-CELLS;

D O I：

10.1371/journal.pone.0036703

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 PPtpn2(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 PPtpn2(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 straindependent.

引用

页数：15

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