Disease relevance of Agtpbp1

• Mutants from the pcd/pcd strain also reacted with continuous tremor, but of lower amplitude and frequency [1].
• The Purkinje Cell Degeneration (Nna1pcd, pcd) mutant mouse is mainly characterized by the complete, primary loss of the Purkinje cells and the secondary, partial, retrograde loss of the granule and inferior olive neurons and is considered a model of human degenerative ataxia [2].
• Increased susceptibility to constant light in nr and pcd mice with inherited retinal degenerations [3].
• Embryonic cerebellar graft development during acute phase of gliosis in the cerebellum of pcd mutant mice [4].

High impact information on Agtpbp1

• Fetal grafts of normal cerebellar tissue were implanted into the cerebellum of Purkinje cell degeneration mutant mice (pcd/pcd), a model of adult-onset recessively inherited cerebello-olivary atrophy, in an attempt at correcting their cellular and motor impairment [5].
• These neurons migrate to their proper domains and, inducing axonal sprouting of specific populations of host neurons, they become integrated synaptically within the pcd cerebellar cortex [6].
• Grafting experiments carried out on the cerebellum of the adult pcd (Purkinje-cell-degeneration) mutant mouse (an animal model of hereditary degenerative ataxia) reveal that embryonic Purkinje cells, by some unknown sorting mechanism, selectively invade the deprived cerebellar cortex [6].
• Embryonic Purkinje cells (PCs) from cerebellar primordia grafted in adult pcd mutant cerebellum replace missing PCs of the host, and become synaptically integrated into the defective cerebellar circuit [7].
• In the cerebellum of Purkinje cell-deficient mutants, such as (pcd/pcd) and lurcher (Lc/+) where Purkinje cells are lost, GlcNAc-Tr was absent, but the other three glycosyltransferase were not severely affected [8].

Biological context of Agtpbp1

• Site of pcd gene action and Purkinje cell mosaicism in cerebella of chimaeric mice [9].
• Mapping of the Sca1 and pcd genes on mouse chromosome 13 provides evidence that they are different genes [10].
• Horizontal vestibuloocular reflex (VOR) head velocity estimation in Purkinje cell degeneration (pcd/pcd) mutant mice [11].
• Behaviorally, pcd homozygotes manifest ataxic signs beginning at 3-4 wk of age [12].
• The presence of a readily detectable genetic mutation in pcd5J confirms that Nna1 loss-of-function alone underlies the broad pcd phenotype and will facilitate further studies of how Nna1 loss-of-function produces neurodegeneration and defective spermatogenesis in pcd mice [13].

Anatomical context of Agtpbp1

• Immunohistochemistry of the cerebella of neurological mutant mice indicated that the Purkinje cells of reeler, weaver, and pcd mutant mice retain the ability to produce a large amount of P400 protein [14].
• Similar to pcd mice, somatal Parv in lurcher mutants increased massively throughout the cerebellar nuclei [15].
• These results show that while head velocity estimation in mice, as in primates, depends on the cerebellum, pcd/pcd mutant mice develop velocity estimation without a functional cerebellar cortex [11].
• Both wild-type and pcd/pcd mice showed a compensatory average VOR eye velocity, or bias, during constant velocity horizontal axis rotations, evidence of central neural processing of otolith afferent signals to create a signal proportional to head angular velocity [11].
• A light microscopic study and cell counts of the inferior olivary nucleus (ION) were performed in the Purkinje cell degeneration mutant mouse (pcd/pcd) [16].

Associations of Agtpbp1 with chemical compounds

• No incorporation of 14C-leucine to the position of P400 protein was found in the nervous and pcd mutant mice where no Purkinje cells and no P400 protein are present [17].
• In this article we report that pcd5J results from the insertion of a single GAC triplet encoding an aspartic acid residue at position 775 of Nna1 [13].
• However, since degeneration led to a reduction in cerebellar weight, the norepinephrine concentration was increased in pcd mutants [18].

Physical interactions of Agtpbp1

• The Purkinje cell degeneration 5J mutation is a single amino acid insertion that destabilizes Nna1 protein [13].

Regulatory relationships of Agtpbp1

• Cerebellar grafts transplanted into the pcd cerebellum expressed only GluRB and GluRC mRNAs, suggesting that donor cells express the appropriate subunits normally expressed by Purkinje neurons [19].

Other interactions of Agtpbp1

• Similar distribution of the c-Kit protein was observed in cerebella of mutant mice in which the Purkinje cell (pcd) or the granular cell layer (weaver) is missing [20].
• These findings clearly demonstrate that bilateral transplants of fetal Purkinje cells have functional effects on motor performance in the pcd model of hereditary cerebellar ataxia [12].
• This assignment rules out the direct involvement of the rhodopsin gene in the known mouse mutations that produce retinal degeneration, including retinal degeneration slow (rds, chromosome 17), retinal degeneration (rd, chromosome 5), Purkinje cell degeneration (pcd, chromosome 13), and nervous (nr, chromosome 8) [21].
• Therefore, after the cerebellar neurodegeneration, there was an overall decrease in IGF-I gene expression in pcd mice [22].
• A slight, but significant, reduction in GD1a concentration occurred only in older pcd/pcd mice, consistent with previous findings in weaver and staggerer mice that GD1a is enriched in mature granule cells [23].

Analytical, diagnostic and therapeutic context of Agtpbp1

• We used quantitative autoradiography of [3H]CNQX (200 nM), [3H]muscimol (13 nM), and [3H]flunitrazepam (10 nM) binding to study the distribution of non-NMDA and GABA(A) receptors in the cerebellum of pcd mutant mice with unilateral cerebellar grafts [24].
• In the deep nuclei of pcd mutants with unilateral cerebellar grafts, [3H]muscimol binding was 31% lower in the grafted side than in the contralateral nongrafted side at 37 days after transplantation; [3H]flunitrazepam binding was also lower in the grafted side by 15% compared to the nongrafted side [24].

References