Phenotypes Associated with This Genotype

Genotype
MGI:3640134

• Allelic Composition: Glb1^tm1Jmat/Glb1^tm1Jmat
• Genetic Background: involves: C57BL/6 * CBA * ICR

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:43534 )

• death occurs between 7 and 10 months of age

behavior/neurological

abnormal eating behavior ( J:43534 )

• difficulty feeding

limb grasping ( J:43534 )

• when hung upside down by the tail, all four limbs are flexed, earliest appearance involves hind limbs only

tremors ( J:43534 )

• shaking becomes progressively worse

abnormal locomotor activation ( J:43534 )

abnormal gait ( J:43534 )

• gait disturbances by 6-8 months of age

• mild shaking

• often totter with forelimbs flexed and with hind limbs extended and extroverted, tail raised straight upward

decreased vertical activity ( J:43534 )

• rearing and climbing activity becomes less frequent after 4 months of age

decreased locomotor activity ( J:43534 )

• gradually decreasing locomotor activity after 4 months of age

• horizontal movements become slow

paralysis ( J:43534 )

• generalized and progressive paralysis

pup cannibalization ( J:43534 )

♀

growth/size/body

cachexia ( J:43534 )

• become emaciated due to difficulty eating

• half normal body weight at death

reproductive system

reduced fertility ( J:43534 )

• higher incidence of sterility and canibalism

• about half of homozygous pairs able to produce at least one litter

• can be maintained as a homozygous stock

nervous system

abnormal brain morphology ( J:40522 )

• 20-30X normal levels of Gm1 gangliosides

gliosis ( J:102576 )

• severe gliosis at 32 weeks of age

• first in brain stem then throughout the brain

abnormal neuron morphology ( J:40522 , J:43534 , J:102576 )

• ballooning neurons in the central nervous system (J:40522)

• areas of degenerating neurons although brain size and weight are normal (J:43534)

• ballooned neurons most extensive at 24 weeks of age and later (J:102576)

• fine granules in some spinal cord neurons at 3 days of age (J:102576)

• vacuolated neurons in brain stem and spinal cord at 1-2 weeks of age (J:102576)

Purkinje cell degeneration ( J:43534 , J:102576 )

• vacuolation and ballooning at 8 weeks of age but less cytoplasmic expansion than in other areas of the brain (J:102576)

liver/biliary system

abnormal hepatocyte morphology ( J:102576 )

• vacuolation and ballooning of hepatocytes at 2 weeks of age

small liver ( J:43534 )

• liver size smaller than normal

immune system

abnormal macrophage chemotaxis ( J:102576 )

• infiltrations of foamy macrophage in thymus, spleen, sub mucosal layer of intestine, and liver after 4 weeks of age

abnormal lymphopoiesis ( J:43534 )

• vacuolated lymphocytes in peripheral blood

small spleen ( J:43534 )

• somewhat smaller than normal as opposed to expected splenomegaly

renal/urinary system

abnormal renal glomerulus morphology ( J:102576 )

• ballooning of glomerular cells in kidney starting between 2 and 4 weeks of age

skeleton

skeleton phenotype ( J:43534 )

N • no skeletal dysplasia

hematopoietic system

abnormal macrophage chemotaxis ( J:102576 )

• infiltrations of foamy macrophage in thymus, spleen, sub mucosal layer of intestine, and liver after 4 weeks of age

abnormal lymphopoiesis ( J:43534 )

• vacuolated lymphocytes in peripheral blood

small spleen ( J:43534 )

• somewhat smaller than normal as opposed to expected splenomegaly

cellular

abnormal macrophage chemotaxis ( J:102576 )

• infiltrations of foamy macrophage in thymus, spleen, sub mucosal layer of intestine, and liver after 4 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
GM1 gangliosidosis		DOID:3322		J:40522 , J:43534