Treatment of Parkinson's disease model mice with allogeneic embryonic stem cells: necessity of immunosuppressive treatment for sustained improvement.

Objective: The purpose of the present study was to examine the efficacy of transplantation of mouse embryonic stem (ES) into Parkinson's disease (PD) model mice as well as the necessity of immunosuppression in allogeneic donor-host combinations.

Materials And Methods: ES cells, derived from SvJ129 strain mice, were differentiated into tyrosine hydroxylase (TH)-positive neurons in vitro by an embryoid body (EB)-based multistep differentiation method and used as graft cells for PD mice, which were prepared by injection of 6-hydroxydopamine (OHDA) into C57BL/6, BALB/c and C3H/HeN strains. Mice from each strain were divided into Groups 1-3.

Meltrin beta expressed in cardiac neural crest cells is required for ventricular septum formation of the heart.

The heart is divided into four chambers by membranous septa and valves. Although evidence suggests that formation of the membranous septa requires migration of neural crest cells into the developing heart, the functional significance of these neural crest cells in the development of the endocardial cushion, an embryonic tissue that gives rise to the membranous appendages, is largely unknown. Mice defective in the protease region of Meltrin beta/ADAM19 show ventricular septal defects and defects in valve formation.

Impaired fatty acid utilization in thioredoxin binding protein-2 (TBP-2)-deficient mice: a unique animal model of Reye syndrome.

Thioredoxin binding protein-2 (TBP-2) is a negative regulator of thioredoxin and has multiple regulatory functions in cellular redox, growth, differentiation, apoptosis, and aging. To investigate the function of TBP-2 in vivo, we generated mice with targeted inactivation of TBP-2 (TBP-2-/- mice). Here, we show that TBP-2 expression is markedly up-regulated during fasting in wild-type mice, while TBP-2-/- mice were predisposed to death with bleeding tendency, as well as hepatic and renal dysfunction as a result of 48 h of fasting.

Partial correction of abnormal cardiac development in caspase-8-deficient mice by cardiomyocyte expression of p 35.

Baculovirus p 35 protein protects cells from apoptotic cell death by inhibiting caspase activation. We have established transgenic mouse lines specifically expressing p 35 in cardiomyocytes, and primary cardiomyocytes isolated from these mice exhibit resistance to staurosporine-induced apoptosis. In a previous study, we observed defects in heart formation associated with abdominal hemorrhage and cardiomyocyte cell death in caspase-8-deficient animals.

HSF4 is required for normal cell growth and differentiation during mouse lens development.

The heat shock transcription factor (HSF) family consists of three members in mammals and regulates expression of heat shock genes via a heat shock element. HSF1 and HSF2 are required for some developmental processes, but it is unclear how they regulate these processes. To elucidate the mechanisms of developmental regulation by HSFs, we generated mice in which the HSF4 gene is mutated.

Activation of heat shock genes is not necessary for protection by heat shock transcription factor 1 against cell death due to a single exposure to high temperatures.

Heat shock response, which is characterized by the induction of a set of heat shock proteins, is essential for induced thermotolerance and is regulated by heat shock transcription factors (HSFs). Curiously, HSF1 is essential for heat shock response in mammals, whereas in avian HSF3, an avian-specific factor is required for the burst activation of heat shock genes. Amino acid sequences of chicken HSF1 are highly conserved with human HSF1, but those of HSF3 diverge significantly.