Mouse Genome Informatics
hm
    Lystbg/Lystbg
B6.C3Rl-Lystbg
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
tumorigenesis
• a tumor line modified to be sensitive to NK cytotoxicity transplanted in mutants results in increased growth rate, faster induction time and an increased metastatic capability of the tumor
• mutants transplanted with virally and chemically induced leukemias develop palpable, progressively growing tumors faster and at a higher frequency than heterozygous controls

pigmentation
• all mice display giant, irregular melanin granules in retinal and choroidal melanocytes; not observed in control mice
• unlike in control mice where mature eumelanin granules from skin, hair and eye are small, ovoid, deeply pigmented and 1-2 micra in diameter, giant melanin granules present in mutant mice are highly irregular and 2-10 micra in diameter (J:5078)
• melanosomes are obviously enlarged and often aggregated (J:5338)
• all mice display giant and irregular melanin granules in the medulla and cortex of hairs; not observed in control mice

cellular
• abnormal lysosomes with high levels of acid phospahatse activity are detected in 15 of 23 tissues examined, including the liver, kidney, pancreas, cerebral cortex, cerebellum, spinal cord, bone marrow, peripheral blood, jejunum, as well as the thyroid, adrenal, gastic, lacrimal, submaxillary glands and sweat glands of the footpad (J:5338)
• anomalous lysosomes are enlarged, often more variable in size and shape and show a tendency to aggregate (J:5338)
• the extent of anomaly varies from one tissue to another and within cells of a given tissue, ranging from extensive enlargement and aggregation of lysosomes in liver to a slight increase in size in sweat glands of the footpad (J:5338)
• the most striking alterations occur in liver parenchymal cells, kidney proximal tubule cells, Purkinje cells of cerebellum, and granulocytes of bone marrow and peripheral blood; no acid phosphatase activity was detected in melanocytes of the eye and skin where melanin granules have not been established as lysosomes (J:5338)
• electron microscopy of liver and kidney revealed enlarged lysosomes containing numerous lipid-like inclusions (J:5338)
• no alterations in lysosomal morphology are detected in striated muscle, duodenum, esophagus, epididymis, spleen or spleen node (J:5338)
• mutants exhibit fusion of newly formed lysosomes in the promocytes and neutrophilic progranulocytes and in mature monocytes, neutrophils, and eosinophils, resulting in fewer but greatly enlarged lysosomes (J:5514)
• androgen-stimulated mutants exhibit an accumulation of giant glucuronidase-containing lysosomes in tubule cells near the croticomedullary boundary of the kidney
• mutants secrete fewer units of glucuronidase, beta-galactosidase, and hexosaminidase than controls
• androgen-treated mutants secrete only 1/3-1/4 as much of the above lysosomal enzymes as controls
• androgen-stimulated mutants exhibit an accumulation of the lysosomal enzymes, beta-glucuronidase, beta-galactosidase, and N-acetyl-beta-D-glucosaminidase (hexosaminidase) in the kidneys, indicating defective process of extruding lysosomal enzymes through the plasma membrane of kidney tubule cells

hematopoietic system
• all mice display giant granules in lymphocytes from peripheral blood and bone marrow, with an inner round density; not observed in control mice
• giant granules are found in a small percentage of cells, usually only 1 or 2 within a cell
• all mice display giant granules in eosinophils from peripheral blood and bone marrow; not observed in control mice
• giant granules are found in a small percentage of cells, usually only 1 or 2 within a cell
• giant granules are highly irregular and contain excessive numbers of clumped "crystalloids"
• all mice display giant granules in neutrophils from peripheral blood and bone marrow; not observed in control mice
• giant granules are found in a small percentage of cells, usually only 1 or 2 within a cell
• spleen cells fail to lyse a variety of natural killer cell sensitive targets, indicating impaired NK cytolysis (J:6213)
• natural killer cell lysis activity toward tumor cells is impaired (J:6302)
• generation of cytotoxic T lymphocytes (CTLs) in response to alloimmune challenge in vivo or in vitro is impaired

immune system
• all mice display giant granules in lymphocytes from peripheral blood and bone marrow, with an inner round density; not observed in control mice
• giant granules are found in a small percentage of cells, usually only 1 or 2 within a cell
• all mice display giant granules in eosinophils from peripheral blood and bone marrow; not observed in control mice
• giant granules are found in a small percentage of cells, usually only 1 or 2 within a cell
• giant granules are highly irregular and contain excessive numbers of clumped "crystalloids"
• all mice display giant granules in neutrophils from peripheral blood and bone marrow; not observed in control mice
• giant granules are found in a small percentage of cells, usually only 1 or 2 within a cell
• spleen cells fail to lyse a variety of natural killer cell sensitive targets, indicating impaired NK cytolysis (J:6213)
• natural killer cell lysis activity toward tumor cells is impaired (J:6302)
• generation of cytotoxic T lymphocytes (CTLs) in response to alloimmune challenge in vivo or in vitro is impaired
• inflammation with infiltration of lymphocytes and macrophages in aged mice

renal/urinary system
• androgen-stimulated mutants exhibit an accumulation of giant glucuronidase-containing lysosomes in tubule cells near the croticomedullary boundary of the kidney
• lower levels of urinary lysosomal enzymes
• total weight of kidney is higher in mutants than in wild-type mice after androgen treatment

nervous system
• infrapyramidal mossy fiber layers within area CA3 of the hippocampus appear to consist of discontinuous clumpings of diffusely scattered small bundles
• infrapyramidal mossy fiber bundles originate from unrelated areas of the dentate gyrus instead of within the suprapyramidal mossy fiber layers as in controls
• the pyramidal cell layer is distorted within the CA3 area and appears as cell free-spaces within the cell layer or as few pyramidal cells ectopically scattered in the stratum orients
• a few pyramidal cells are ectopically scattered in the stratum orients
• arrangement of the Bergmann cells is more dispersed than in controls and a few ectopic Bergmann cells are located in the upper portion of the molecular layer
• ectopic Purkinje cells, mostly found in the lower half of the molecular layer as single cells
• clusters of ectopic granule cells in the molecular layer

behavior/neurological
• mutants exhibit increased sleeping time and prolonged bleeding times after treatment with pentobarbital, tribromoethanol, or the steroid anesthetic alphaxalone
• mice exhibit an inverted optokinetic nystagmus in response to stimulation of only the temporal retina
• mice exhibit eye movements with a vertical component in response to horizontally moving, full-field stimuli

hearing/vestibular/ear
• mice exhibit an inverted optokinetic nystagmus in response to stimulation of only the temporal retina
• mice exhibit eye movements with a vertical component in response to horizontally moving, full-field stimuli

homeostasis/metabolism
• lower levels of urinary lysosomal enzymes

integument
• all mice display giant and irregular melanin granules in the medulla and cortex of hairs; not observed in control mice

respiratory system
• inflammation with infiltration of lymphocytes and macrophages in aged mice
• progressive cytoplasmic foamy changes in type II pneumocytes from P0 to 24 months of age, increasing in terms of both the affected cell number and degree of severity as mice age
• marked swelling and degenerative changes of type II pneumocytes (referred to as "giant lamellar body degeneration" or GLBD) in aged mice
• most lamellar bodies are increased in size at P0
• numerous giant-sized lamellar bodies are often fused with each other in aged mice, often resulting in cellular distension and degeneration
• enlarged air spaces in aged mice
• slight fibrosis in aged mice with prominent GLBD
• no evidence of interstitial change in younger mice with only GLBD
• patchy areas of alveolar collapse associated with marked GLBD, lymphocytic infiltration and slight fibrosis in aged mice

Mouse Models of Human Disease
OMIM IDRef(s)
Chediak-Higashi Syndrome; CHS 214500 J:4978 , J:5078 , J:5338 , J:5405 , J:5471 , J:5514 , J:5590 , J:6302