Immune abnormality in relation to nonimmune diseases in sam mice

Hosono, Masamichi; Hanada, Keita; Toichi, Eiko; Naiki, Hironobu; Higuchi, Kenichi; Hosokawa, Tomokazu

doi:10.1016/s0531-5565(96)00070-8

Cited by 25 publications

(21 citation statements)

References 26 publications

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“…3 Among animal models of presbycusis, the SAMP1 mouse is most suitable by virtue of its progressive hearing loss with an onset at an early age, as well as accelerated senescence in an inherited pattern. 4,5 Molecular studies, such as transfer experiments of the Akv-1 gene 4 and apoA-II gene, 6 are in progress. Age-accelerated somatic mutations were also found in the hypoxanthine phosphoribosyl transferase (Hprt) locus of splenic lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

“…SAMP1 mice have been reported to have some gene abnormalities which reduce the host immunity. 4,7 Therefore, gene therapy using autologous HSCs may also have a therapeutic effect on both immunological dysfunctions and hearing impairment.…”

Section: Discussionmentioning

confidence: 99%

“…11 Since age-related changes in the immune system appear relatively early in life, it is suggested that immune impairment may be a cause of age-related disease. 4 We have previously shown that the dysfunctions of immunocompetent cells, but not abnormalities in the cochlea, cause the development of autoimmune sensori-neural hearing loss resulting from the deposits of autoantibodies to cochlea in autoimmune-prone MRL/lpr mice. 12 We have also demonstrated that the hearing loss and cochlear pathology are derived from defects in the bone marrow cells; BMT can be used to prevent the development of the sensori-neural hearing loss.…”

mentioning

confidence: 96%

“…4,5 Molecular studies, such as transfer experiments of the Akv-1 gene 4 and apoA-II gene, 6 are in progress. Age-accelerated somatic mutations were also found in the hypoxanthine phosphoribosyl transferase (Hprt) locus of splenic lymphocytes.…”

mentioning

confidence: 99%

“…Age-accelerated somatic mutations were also found in the hypoxanthine phosphoribosyl transferase (Hprt) locus of splenic lymphocytes. 7 This mouse strain shows an early occurrence of accelerated dysfunctions of immunocompetent cells, particularly T cells, 4,8 followed by accelerated hearing impairment, 5 the loss of physical activity, alopecia, periophthalmic lesions, and increased lordokyphosis of the spine, as well as spontaneous age-associated amyloidosis and shortened lifespan. 9,10 Early production of autoantibodies against DNA, thymocytes and collagen type II and the early deposition of immune complexes in the glomeruli of the kidney have been demonstrated in these mice.…”

mentioning

confidence: 99%

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Prevention of accelerated presbycusis by bone marrow transplantation in senescence-accelerated mice

Iwai

Lee

Inaba

et al. 2001

Bone Marrow Transplant

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Summary:A substrain of the senescence-accelerated mouse (SAM), the SAMP1 mouse, is an animal model for accelerated senescence including the age-related acceleration of both immunological dysfunction and hearing loss caused by the impairment of spiral ganglion cells. In the present study, we examine whether the accelerated presbycusis can be prevented by allogeneic BMT. Young SAMP1 (H-2 k ) mice were irradiated with 9 Gy and then reconstituted with bone marrow cells from normal BALB/c (H-2 d ) mice. Allogeneic BMT was found to prevent the development of immunological dysfunction, hearing loss, and apoptosis of spinal ganglion cells in SAMP1 mice. These findings indicate that some types of accelerated presbycusis do not result from defects in the cochlea, but do from defects in the hematopoietic stem cells (HSC) and immunocompetent cells derived from the HSC. If this is the case, either allogeneic BMT, which replaces abnormal HSC with normal HSC and reconstructs a normal immune system in the recipients, or autologous BMT using genetically modified bone marrow cells, could become a new strategy for the treatment of presbycusis. Bone Marrow Transplantation (2001) 28, 323-328. Keywords: presbycusis; spiral ganglion cell; bone marrow transplantation; T lymphocyte; apoptosis There has been no strategy for the prevention and treatment of presbycusis. There is a widespread presumption based on clinical observations that presbycusis is an inherited disorder, and that genetic factors may influence both the rate and severity of the hearing loss. 1,2 However, the genetic factors are still unclear, since more than one pathologic process may be acting upon the auditory system, 1 and environmental factors are also involved. 3 Among animal models of presbycusis, the SAMP1 mouse is most suitable by virtue of its progressive hearing loss with an onset at an early age, as well as accelerated senescence in an inherited pattern. 4,5 Molecular studies, such as transfer experiments of the Akv-1 gene 4 and apoA-II gene, 6 are in progress. Age-accelerated somatic mutations were also found in the hypoxanthine phosphoribosyl transferase (Hprt) locus of splenic lymphocytes. 7 This mouse strain shows an early occurrence of accelerated dysfunctions of immunocompetent cells, particularly T cells, 4,8 followed by accelerated hearing impairment, 5 the loss of physical activity, alopecia, periophthalmic lesions, and increased lordokyphosis of the spine, as well as spontaneous age-associated amyloidosis and shortened lifespan. 9,10 Early production of autoantibodies against DNA, thymocytes and collagen type II and the early deposition of immune complexes in the glomeruli of the kidney have been demonstrated in these mice. 11 Since age-related changes in the immune system appear relatively early in life, it is suggested that immune impairment may be a cause of age-related disease. 4 We have previously shown that the dysfunctions of immunocompetent cells, but not abnormalities in the cochlea, cause the development of autoimmune sensori-neural hearin...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 96%

mentioning

confidence: 99%