Disease relevance of Ky

• The ky mouse mutant exhibits a primary degenerative myopathy preceding chronic thoraco-lumbar kyphoscoliosis [1].
• Muscle hypertrophy in response to increasing demand is deficient in the ky mutant, whereas adaptive fibre type shifts take place [1].
• The identification of the ky gene will allow detailed analysis of the impact of primary myopathy on idiopathic scoliosis in mice and man [1].
• Altogether, the data presented suggest that the ky muscular dystrophy develops by a distinctive pathogenic mechanism [2].
• Subsets of transgenic T cells that recognize CD1 induce or prevent murine lupus: role of cytokines [3].

Psychiatry related information on Ky

• Changes in GLUT expression produced by training in an operant conditioning task were measured in the brain of CD1 mice [4].
• Strain differences were observed in avoidance learning, with BALB, DBA, C57 x SJL and CD1 mice showing significantly better avoidance learning than C57 mice, which were better than SJL mice [5].
• THA-C8 (0.1-5 mg/kg) significantly reduced spontaneous locomotor activity in CD1 mice at a dose of 3 mg/kg [6].
• The HPA system during the postnatal development of CD1 mice and the effects of maternal deprivation [7].
• Spatial and visual discrimination learning in CD1 mice: partial analogy between the effect of lesions to the hippocampus and the amygdala [8].

High impact information on Ky

• Mouse CD1-specific NK1 T cells: development, specificity, and function [9].
• CD1-deficient mice were found to lack this lymphocyte subset, but they could nevertheless mount a protypical TH2 response; after immunization with antibody to immunoglobulin D (IgD), CD1-deficient mice produced IgE [10].
• CD1 molecules are distantly related to the major histocompatibility complex (MHC) class I proteins [11].
• In mice, an entire subset of alpha beta thymocytes with a unique phenotype was found to be CD1-specific [12].
• Endosomal trafficking is an essential component of the CD1 pathway of lipid antigen presentation to T cells [13].

Chemical compound and disease context of Ky

• However, priming with high doses of LPS caused mortality of severe combined immunodeficiency, NKT cell-deficient, and CD1-deficient mice, indicating a major contribution of NKT cells to the Shwartzman reaction elicited by low doses of LPS, whereas at higher doses of LPS NK cells play a prominent role [14].
• Weanling CD1 mice (n=5) were injected with alloxan (50 mg/kg i.v.) to induce IDDM [15].
• Irritant dermatitis was induced by applying phorbol 12-myristate-13-acetate (TPA) to the surface of the ears of CD1 mice, followed by treatment with 22ROH, 25OH, GW3965, or vehicle alone [16].
• The present study examined whether NK cells control 1,2-dimethylhydrazine (DMH)-induced hyperplasia of the duodenal crypt in CD1 mice [17].
• Photodynamic therapy (PDT), locally applied to solid C6 rat glioma tumors in the foot of CD1 nude mice, eradicated the primary tumor and also decreased the rate of groin and lung metastases [18].

Biological context of Ky

• The Ky protein has a putative key function in muscle development and has homologues in invertebrates, fungi and a cyanobacterium [19].
• The ky locus has previously been localized to a small region of mouse chromosome 9 and we have now identified the gene and the mutation underlying the kyphoscoliotic mouse [1].
• Upregulation of uncoupling proteins 1 and 2 is a unique molecular signature of the ky muscular dystrophy and was further characterised at the protein level [2].
• Breeding experiments confirmed that a hereditary form of kyphoscoliosis in the BDL strain mouse was due to an autosomal recessive gene (ky) [20].
• Muscles of ky/ky homozygote mice exhibit neonatal muscle fiber necrosis and regeneration with subsequent motor nerve sprouting and development of a prominent kyphoscoliosis from approximately 100 days onward [21].

Anatomical context of Ky

• The ky transcript encodes a novel protein that is detected only in skeletal muscle and heart [1].
• The histopathology of the ky mutant suggests that Ky protein activity is crucial for normal muscle growth and function as well as the maturation and stabilization of the neuromuscular junction [1].
• The ky mouse mutant exhibits a degenerative muscle disease resulting in chronic deformation of the spinal column [22].
• Two studies in this issue of Immunity take a detailed look at factors affecting the localization of mouse CD1 proteins to the endocytic system of antigen-presenting cells [23].
• In vitro, thymic dendritic cells (DCs) from cathepsin S(-/-) mice exhibit defective presentation of the CD1-restricted antigen, alpha-galactosylceramide (alpha-GalCer) [24].

Associations of Ky with chemical compounds

• For members of the CD1 family of beta(2)-microglobulin-associated lipid-presenting molecules, tyrosine-based motifs in the cytoplasmic tail and invariant chain (Ii) govern glycoprotein trafficking through endosomal compartments [25].
• Similarly, 4% of the embryos from pregnant CD1 mice on days 8 and 12 of gestation produced a significant amount of nitrate, which again correlated with the low incidence of resorption observed in these mice [26].
• Subsequently, a slight lateral shift (>1 A) of the galacturonosyl head group is noted at the CD1 surface compared with the galactose of alpha-GalCer [27].
• Urogenital carcinogenesis in female CD1 mice induced by in utero arsenic exposure is exacerbated by postnatal diethylstilbestrol treatment [28].
• Male CD1 mice (40 per group) received dimethylhydrazine (30 mg/kg/week x 6 weeks, s.c.) and various schedules of DFMO, 1% in drinking water: Group A, none; Group B, following dimethylhydrazine treatment; Group C, during dimethylhydrazine treatment; and Group D, continuously throughout the study [29].

Other interactions of Ky

• Molecular phenotyping of the mouse ky mutant reveals UCP1 upregulation at the neuromuscular junctions of dystrophic soleus muscle [2].
• Mechanical power and myosin composition of soleus and extensor digitorum longus muscles of ky mice [21].

Analytical, diagnostic and therapeutic context of Ky

• Using surface plasmon resonance, we show that at neutral pH, mouse CD1 and human CD1d bind to immobilized alpha-GalCer, unlike human CD1b, which requires acidic pH for lipid antigen binding [30].
• We transferred the NIF gene into CD1 mouse lungs by intravenous injection of cationic liposomes to study the effects of in vivo NIF expression on LPS-induced lung PMN sequestration and the development of lung injury [31].
• Moreover, vaccination cured half of the CD1 and the majority of the MCP1 KO mice [32].
• The progeny of a cross between CD1-derived TGF-alpha transgenic (MT42) and C57BL/6 mice exhibited no reduction in tumor burden (83%); however, the incidence of tumor formation in MT42 x FVB/N offspring was substantially lower (19%) [33].
• CD1 mice were made septic by the cecal ligation and puncture method and treated postoperatively with anti-CD40 Ab [34].

References