title: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Florian
authors.initials: F
authors.lastname: Wiede
authors.forename: Sock Hui
authors.initials: SH
authors.lastname: Chew
authors.forename: Catherine
authors.initials: C
authors.lastname: van Vliet
authors.forename: Ingrid J
authors.initials: IJ
authors.lastname: Poulton
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kyparissoudis
authors.forename: Tedjo
authors.initials: T
authors.lastname: Sasmono
authors.forename: Kim
authors.initials: K
authors.lastname: Loh
authors.forename: Michel L
authors.initials: ML
authors.lastname: Tremblay
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Sims
authors.forename: Tony
authors.initials: T
authors.lastname: Tiganis
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D001846:Bone Development; D016723:Bone Remodeling; D003433:Crosses, Genetic; D004920:Erythropoiesis; D006965:Hyperplasia; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; C516653:Ptpn2 protein, mouse