Prop1

The gene apparently responsible for a heritable form of murine pituitary-dependent dwarfism (Ames dwarf, df) has been positionally cloned, identifying a novel, tissue-specific, paired-like homeodomain transcription factor, termed Prophet ..

..The Ames dwarf (df) mouse displays a similar phenotype, and appears to be epistatic to Snell and Jackson dwarfism...

The Ames dwarf mouse transmits a recessive mutation (df) resulting in a profound anterior pituitary hypocellularity due to a general lack of thyrotropes, somatotropes and lactotropes...

Mutations in the PROP1 transcription factor gene lead to reduced production of thyrotropin, GH, prolactin, and gonadotropins as well as to pituitary hypoplasia in adult humans and mice...

Mutations in Prophet of PIT1 (Prop1), one of several homeodomain transcription factors that are required for the development of the anterior pituitary gland, are the predominant cause of MPHD (multiple pituitary hormone deficiency) in ..

..Mutations in the transcription factor Prop1 interfere with pituitary growth and cell specification, although the mechanism is unknown...

....

The 'paired'-like homeodomain transcription factor Prop1 is essential for the expansion of the pituitary primordia and for the differentiation and/or function of the hormone-producing cells of the anterior pituitary gland...

Deficiencies in the homeobox transcription factors LHX4 and PROP1 cause pituitary hormone deficiency in both humans and mice...

..expansion of Rathke's pouch and maintaining expression of the fetal-specific transcription factors Hesx1 and Prop1. At later stages Pitx2 is necessary for specification and expansion of the gonadotropes and Pit1 lineage within ..

The prophet of Pit1 (PROP1) gene is essential for normal gonadotropin production in both humans and mice...

....

b>Ames dwarf (df) is an autosomal recessive mutation characterized by severe dwarfism and infertility. This mutation provides a mouse model for panhypopituitarism...

Mutations in the prophet of PIT1 gene (PROP1) are the most common cause of multiple pituitary hormone deficiency in humans; however, the mechanism of PROP1 action is not well understood...

..Later, Pit-1 and hypothalamic neuropeptides act sequentially to regulate marker gene transcription and cell proliferation. These results establish the time of df action in a cascade of genes that regulate pituitary ontogeny...

..Our research has revealed a role for Six3 in normal pituitary development, which has likely been conserved during evolution as SIX3 is also expressed in the pituitary gland of the human embryo...

..However, these mouse models are already providing new information about the mechanism underlying mammalian aging...

..In addition, from the standpoint of aging research, these statistical approaches have appealing properties and provide valuable tools for the analysis of survivorship data...

..The insulin-stimulated phosphorylation of the insulin receptor (IR) was reduced by 55% in Ames dwarf mice, while IR receptor protein content was not altered...

..Together, these results suggest that the I26T mutation yields a hypomorphic allele, whereas R160C produces a null allele and, consequently, a more severe phenotype in both mice and humans...

Growth hormone (GH) is an anabolic hormone that regulates growth and metabolism. Ames dwarf mice are natural mutants for Prop1, with impaired development of anterior pituitary and undetectable levels of circulating GH, prolactin and TSH...

In the present study we have used hypopituitary Ames dwarf mice, which lack GH, prolactin and TSH, to investigate the consequences of the deficiency of these hormones on glucose homeostasis and on the initial components of the insulin ..

..We have evidence that long-living GH-deficient Ames dwarf mice have enhanced antioxidant protection in the periphery but the protection in the central nervous system is ..

..b>Prop1 and Hesx1 are also important for normal shape of the pituitary primordium, but their expression is unaltered in ..

..on a low isoflavone or a high isoflavone soy protein isolates in normal, growth-hormone receptor knockout and Ames dwarf, and Prop 1 (df) mice that are hypoinsulinemic, insulin-sensitive, and exceptionally long-lived, as well as in ..

..Accordingly, the present observations provide a novel view to understand the hypogonadism caused by Prop-1 defects at the molecular level through the regulatory mechanism of alphaGSU and FSHbeta gene expressions...

..gender-independent effects of lifespan-extending mutations of the GH/IGF-I axis is currently lacking. The Ames dwarf mice (prop1(df/df)) are GH, prolactin and thyroid-stimulating hormone deficient and exhibit an increase in mean ..

..We show here that similar resistance profiles are seen in fibroblast cells derived from a related mutant, the Ames dwarf mouse, and that cells from growth hormone receptor-null mice are resistant to H(2)O(2), paraquat, and UV but not ..

b>Ames dwarf mice are a model of retarded aging and extended longevity and display enhanced insulin sensitivity. Caloric restriction (CR) and the dwarf mutation have additive effects on lifespan...

..Pituitary cell differentiation and morphology appeared normal in the Rgs2 mutant animals, suggesting that other Rgs family members with similar activities may be present in the developing pituitary...

..Hypopituitary Ames dwarf mice have extended longevity and exhibit many symptoms of delayed aging, although various aspects of immune ..

..We conclude that TH supplement administered during the critical period of hearing development in mice can prevent deafness associated with congenital hypothyroidism of heterogeneous genetic etiology...

..Multiple trophic factors including IGF-I have been demonstrated to regulate hippocampal neurogenesis. Ames dwarf mice live considerably longer than normal animals and maintain physiological function at youthful levels, ..

..Thus, TCF4 is necessary both intrinsically and extrinsically to Rathke's pouch to ensure the proper growth of the pituitary gland...

Pit1 null (Snell dwarf) and Proph1 null (Ames dwarf) mutant mice lack GH, PRL and TSH. Snell and Ames dwarf mice also exhibit reduced IGF-I, resistance to cancer and a longer lifespan than control mice...

Mutations in the transcription factors PIT1 (pituitary transcription factor 1) and PROP1 (prophet of Pit1) lead to pituitary hormone deficiency and hypopituitarism in mice and humans...

..It is suggested that Tbx19, depending on the presence of synergizing transcription factors, can activate POMC gene expression and repress the alpha glycoprotein subunit and thyroid-stimulating hormone beta promoters...

..The data indicate that Pit-1 is necessary for the specification of the phenotype of three cell types in the anterior pituitary, and directly link a transcription factor to commitment and progression events in mammalian organogenesis...

..For comparison, similar studies were performed in GH and PRL deficient Ames dwarf mice in which plasma gonadotropin levels are known to be reduced...

..In order to determine whether this deficit in adult Ames dwarf mice is congenital or arises postnatally, brains of dwarf (df/df) and normal (DF/?) littermate mice were ..

b>Ames dwarf mice have a recessive defect that results in affected mice (df/df) with extremely hypocellular anterior pituitaries that generally lack somatotropes, lactotropes, and thyrotropes...

..The results suggest that chronic GH deficiency is accompanied by increased translation as well as transcription of GHRH...

..One such model, the Ames dwarf mouse (df/df), has arisen from an autosomal recessive mutation in which GH-, prolactin- (PRL), and thyroid-..

..GH treatment of the Snell mouse resulted in an increase in somatomedin activity to normal levels...

..It was concluded that in the homozygous condition, both types of dwarf alleles result in failure of the pituitary to initiate GH and PRL synthesis...

..The lack of PRL-containing cells in the dwarf mouse pituitary may explain why peripheral PRL levels in this animal are below those measured in hypophysectomized mice...

Restriction endonuclease analysis of genomic DNA was carried out for three types of dwarf mice (Little, Ames dwarf and Snell dwarf) that have genetic defects in GH expression...

..The alpha- and delta-cells normally found in the islets of Langerhans are rare and disordered. Well-vascularized beta-cell tumours arise in mice harbouring and inheriting these hybrid oncogenes...

..The Ames dwarf (df) exhibits a phenotype identical to that of Pit-1 mutated mice but the defective gene has been mapped to a ..

In the spontaneous mutant Ames dwarf mouse, GH deficiency coincides with a dramatic increase in the expression of both mRNA and peptide for stimulatory GHRH and reduced expression of GH-inhibitory somatostatin (SRIH) mRNA and peptide...

b>Ames dwarf mice, homozygous for the df allele at the Prop1 locus, live 40% to 70% longer than nonmutant siblings and represent the first single-gene mutant that extends life span in a mammal...

..However, little is known about the Ames dwarf mouse, which has a Prop-1 gene mutation resulting in deficiencies in growth hormone, thyroid-stimulating hormone,..

..of mZn-16 expression by RT-PCR showed that the mRNA is, produced at similar levels in normal and GH-deficient Ames dwarf (Prop-1 <df-/->) mouse pituitaries at postnatal day 1...

..We suggest that the transient dorsal expression of Pax6 is essential for establishing a sharp boundary between dorsal and ventral cell types, based on the inhibition of Shh ventral signals...

..Two genetic mouse models of aging, the Ames dwarf and growth hormone (GH) transgenic, suggest that hormone levels may play a role in antioxidative defense and ..

..and cellular composition of the thyroid was examined in genetically thyrotropin (TSH)-deficient female Ames dwarf mice (df/df) to reveal whether estrogen might act independently from TSH...

..Because Ames dwarf mice (dwarfs) live approximately 1 year longer than their larger normal sex- and age-matched siblings (normals), ..

..The aim of this study was to investigate the early changes in kidney IGF-I in experimental diabetes in mice transgenic for bovine GH and in genetically GH-deficient Ames dwarf mice.

....

..glands of little mice showed a deficiency or absence of secretory granules within somatotropes, while Snell and Ames dwarf pituitaries lacked identifiable somatotropes...

Hypopituitary Ames dwarf mice have low circulating growth hormone (GH)/IGF-I levels, and they have extended longevity and exhibit many symptoms of delayed aging...

b>Ames dwarf mice live 50-64% longer and exhibit upregulated antioxidative defenses and lower cellular damage when compared to age-matched wild-type littermates...

..NPY neuronal number in adult Ames dwarf mice (1048 +/- 104) was significantly (P < 0...

..Normal FOXL2 expression requires the transcription factors Lhx3 and Lhx4 but not of Prop1. Thus, FOXL2 expression is affected by mutations in early pituitary developmental regulatory genes, and its ..

..Studies in our laboratory have suggested that both Ames dwarf and GH receptor/GH binding protein knockout (GH-R-KO) mice do not experience age-induced cognitive aging at the ..

..Thus, Pitx2 is a transcription factor that encodes 'leftness' of the lung...

Development of the hypophysiotropic hypothalamus in PRL-deficient Ames dwarf (df/df) mice was examined for steady state dopamine (DA) by visualization using formaldehyde-induced catecholamine histofluorescence and by quantification using ..

..of growth hormone on processes related to stress resistance and longevity using two long-living mouse strains, Ames dwarf and growth hormone receptor knockout mice...

..Mice with hereditary dwarfism (Ames dwarf) exhibit growth hormone deficiency, delayed aging, enhanced antioxidant defenses and lower oxidative DNA and ..

..of growth hormone on processes related to stress resistance and longevity using two long-living mouse strains, Ames dwarf and growth hormone receptor knockout mice...

..One could infer that a lean body promotes healthy insulin action and a longer life. However, Ames dwarf and GHRKO mice are both hyper-sensitive to injected insulin and long-lived despite an increased or normal volume ..

..We are also seeking support for the presenters of the Special Lecture and the Keynote Lecture who will be traveling to Bregenz from the United States. ..

..Financial assistance will be provided to those in training to encourage their participation in the meeting. ..

..We have recently demonstrated that in one of these models, the Ames dwarf (Prop1df) mouse, CR may extend life beyond the limits achievable with CR or dwarfism alone...

..We are also seeking partial support for the expenses of invited speakers from the United States. ..

..We have shown that caloric restriction (CR) increases longevity in the Ames dwarf mouse, a long-lived hypopituitary mutant, but surprisingly fails to extend longevity in another long-lived ..

..We have shown that caloric restriction (CR) increases longevity in the Ames dwarf mouse, a long-lived hypopituitary mutant, but surprisingly fails to extend longevity in another long-lived ..

..We have shown that caloric restriction (CR) increases longevity in the Ames dwarf mouse, a long-lived hypopituitary mutant, but surprisingly fails to extend longevity in another long-lived ..

..Therefore, future research must synthesize highly efficacious melatonin analogues capable of providing maximum analgesia and hopefully being devoid of addiction liability now associated with currently available narcotics. ..

..The completion of these studies will undoubtedly provide additional items of information on reactive oxygen species-induced damage of mitochondrial DNA and the protective effects of coenzyme Q10(ubiquinol) to minimize it. ..