Structure, chromosomal localization and expression of mouse genes encoding type III Reg, RegIIIα, RegIIIβ, RegIIIγ

Narushima, Yoichi; Unno, Michiaki; Nakagawara, Kan-ichi; Mori, Mitsuko; Miyashita, Hidetoshi; Suzuki, Yuzuru; Noguchi, Naoya; Takasawa, Shin; Kumagai, Tomoko; Yonekura, Hideto; Okamoto, Hiroshi

doi:10.1016/s0378-1119(96)00589-6

Cited by 104 publications

(92 citation statements)

References 29 publications

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“…Equivalent levels of IFN-␥ were secreted by WT and KO CD4 ϩ T cells. Regenerating gene (Reg) was identified as a gene that is upregulated in regenerating pancreatic ␤ islet cells (22). Whereas deletion of the Reg2 gene led to decreased proliferation of the pancreatic ␤ islet cells, NOD mice carrying a Reg2 transgene specifically expressed in the pancreas displayed a significant delay in the onset of diabetes (23).…”

Section: Normal T Cell Populations and Cytokine Production In Nod/il2mentioning

confidence: 99%

IL-21 signaling is critical for the development of type I diabetes in the NOD mouse

Spolski

Kashyap

Robinson

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

188

161

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IL-21 is a pleiotropic type I cytokine that shares the common cytokine receptor ␥ chain and plays important roles for normal Ig production, terminal B cell differentiation to plasma cells, and Th17 differentiation. IL-21 is elevated in several autoimmune diseases, and blocking its action has attenuated disease in MRL/lpr mice and in collagen-induced arthritis. The diabetes-associated Idd3 locus is at the Il2/Il21 locus, and elevated IL-21 was observed in the nonobese diabetic (NOD) mouse and suggested to contribute to diabetes by augmenting T cell homeostatic proliferation. To determine the role of IL-21 in diabetes, Il21r-knockout (KO) mice were backcrossed to NOD mice. These mice were devoid of lymphocytic infiltration into the pancreas, and only 1 of 20 animals had an elevated glucose compared with 60% of NOD mice on a wild-type (WT) background. Although TCR and Treg-related responses were normal, these mice had reduced Th17 cells and significantly higher levels of mRNAs encoding members of the Reg (regenerating) gene family whose transgenic expression protects against diabetes. Our studies establish a critical role for IL-21 in the development of type I diabetes in the NOD mouse, with obvious potential implications for type I diabetes in humans. Reg genes ͉ Th17 cellsH uman type I diabetes is an autoimmune disease that results from the autoreactive destruction of pancreatic ␤ cells and subsequent loss of insulin production (1). Nonobese diabetic (NOD) mice develop a similar disease and serve as a model system for studying the mechanisms involved in the initiation and propagation of the autoimmune response (2). Although it has been established that ␤ islet cell destruction is initiated by proinflammatory CD4 ϩ and CD8 ϩ T cells infiltrating the pancreas, the molecular mechanisms and cytokine pathways that control this process are not fully understood.IL-21 is a type I cytokine (3) that is the most recently discovered member of the family of cytokines that share the common cytokine receptor ␥ chain, ␥ c (4) . ␥ c is also shared by IL-2, IL-4, IL-7, IL-9, and IL-15 and is mutated in humans with X-linked severe combined immunodeficiency (XSCID) (5). IL-21 is produced most abundantly by CD4 ϩ T cells, including Th17 lineage cells (6-8) and natural killer T (NKT) cells (9), and is known to act on both lymphoid and nonlymphoid target cells, thus controlling both innate and adaptive immune responses (4). IL-21 is critical for normal Ig production (10), can cooperatively drive expansion of CD8 ϩ T cells (11), can activate NK cells (12), and drives terminal B cell differentiation into plasma cells (13). IL-21 has been implicated as playing a role in the development of B cell-mediated lupus-like autoimmune disease based on studies in the BXSB-Yaa (13), Sanroque (14), and MRL/lpr mice (15), and treatment with a soluble IL-21R-Fc fusion protein was shown to lead to a partial decrease in disease severity in the MRL/lpr mice (15) and collagen-induced arthritis (16). In experimental allergic encephalitis (EAE), a model for ...

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Section: Normal T Cell Populations and Cytokine Production In Nod/il2mentioning

confidence: 99%

IL-21 signaling is critical for the development of type I diabetes in the NOD mouse

Spolski

Kashyap

Robinson

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

188

161

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“…Rat Reg2 [also known as RegIII␤ in mouse and HIP/ PAP1 in humans (7)] has been reported to play an important role in both the support of motor neurons during development and in the process of axon regeneration through axon-Schwann cell signaling in the adult peripheral nervous system (8,9). Reg2 is a member of a large family of over 17 related genes divided into four subtypes (types I, II, III, and IV) based on the primary structures of the encoded proteins of the genes (10)(11)(12)(13).…”

Section: Schwann Cells ͉ Suckling ͉ Hypoglossal Nerve ͉ Lifmentioning

confidence: 99%

Deletion of the mouse RegIIIβ (Reg2) gene disrupts ciliary neurotrophic factor signaling and delays myelination of mouse cranial motor neurons

Tebar

Géranton

Parsons-Perez

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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A large number of cytokines and growth factors support the development and subsequent maintenance of postnatal motor neurons. RegIII␤, also known as Reg2 in rat and HIP/PAP1 in humans, is a member of a family of growth factors found in many areas of the body and previously shown to play an important role in both the development and regeneration of subsets of motor neurons. It has been suggested that RegIII␤ expressed by motor neurons is both an obligatory intermediate in the downstream signaling of the leukemia inhibitory factor/ciliary neurotrophic factor (CNTF) family of cytokines, maintaining the integrity of motor neurons during development, as well as a powerful influence on Schwann cell growth during regeneration of the peripheral nerve. Here we report that in mice with a deletion of the RegIII␤ gene, motor neuron survival was unaffected up to 28 weeks after birth. However, there was no CNTF-mediated rescue of neonatal facial motor neurons after axotomy in KO animals when compared with wild-type. In mice, RegIII␤ positive motor neurons are concentrated in cranial motor nuclei that are involved in the patterning of swallowing and suckling. We found that suckling was impaired in RegIII␤ KO mice and correlated this with a significant delay in myelination of the hypoglossal nerve. In summary, we propose that RegIII␤ has an important role to play in the developmental fine-tuning of neonatal motor behaviors mediating the response to peripherally derived cytokines and growth factors and regulating the myelination of motor axons.Schwann cells ͉ suckling ͉ hypoglossal nerve ͉ LIF

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“…2 We have reason to believe that the actual target was mouse Reg3␤ (also known as Reg III␤; or PAP, PAP1 and HIP in other species). [3][4][5] As shown in Fig. 1, the polymerase chain reaction (PCR) primers used to genotype the knockout offspring were perfectly matched to the genomic sequence of mouse Reg3␤ gene (access number D63360), which would generate a product of 687 base pairs, similar to the 600 base pairs reported.…”

mentioning

confidence: 73%

“…All the genes have 6 exons and map to a 75-kb region of chromosome 6C, except Reg4. 5,[8][9][10] The literature has used other names, especially when referring to other species, such as HIP, gene expressed in hepatocellular carcinoma/intestine/pancreas; PAP, pancreatitis-associated protein; PSP, pancreatic stone protein; PTP, pancreatic thread protein; and RELP, regenerating protein-like protein. The GenBank access numbers refer to genomic, cDNA, and protein sequences, respectively.…”

Section: Jun-li Liu Wei Cui Fraser Laboratories For Diabetes Researchmentioning

confidence: 99%

Which gene, Reg2 or Ref3β, was targeted that affected liver regeneration?

Liu¹,

Cui²

2007

Hepatology

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Structure, chromosomal localization and expression of mouse genes encoding type III Reg, RegIIIα, RegIIIβ, RegIIIγ

Cited by 104 publications

References 29 publications

IL-21 signaling is critical for the development of type I diabetes in the NOD mouse

IL-21 signaling is critical for the development of type I diabetes in the NOD mouse

Deletion of the mouse RegIIIβ (Reg2) gene disrupts ciliary neurotrophic factor signaling and delays myelination of mouse cranial motor neurons

Which gene, Reg2 or Ref3β, was targeted that affected liver regeneration?

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