Phenotypes associated with this allele

• Allele Symbol: Gba1^tm2Karl
• Allele Name: targeted mutation 2, Stefan Karlsson
• Allele ID: MGI:3764510
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gba1^tm2Karl/Gba1^tm2Karl	involves: 129S1/Sv * 129X1/SvJ	MGI:3764514
cn2	Gba1^tm2Karl/Gba1^tm2Karl Tg(KRT14-cre)8Brn/?	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:3764515

Genotype
MGI:3764514

hm1

• Allelic Composition: Gba1^tm2Karl/Gba1^tm2Karl
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

Gba1^tm2Karl/Gba1^tm2Karl (upper left) mice display a lethal skin phenotype whileGba1^tm2Karl/Gba1^tm2Karl Tg(KRT14-cre)8Brn/? (lower) mice display paralysis

mortality/aging

neonatal lethality, complete penetrance ( J:127108 )

• mice die within a few hours of birth with a similar skin phenotype as observed in other Gba defective mice

integument

abnormal skin condition ( J:127108 )

• mice die within a few hours of birth with a similar skin phenotype as observed in other Gba defective mice

Genotype
MGI:3764515

cn2

• Allelic Composition: Gba1^tm2Karl/Gba1^tm2Karl; Tg(KRT14-cre)8Brn/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

Gba1^tm2Karl/Gba1^tm2Karl Tg(KRT14-cre)8Brn/? mice display a severe and rapidly progressive neurological disease

mortality/aging

postnatal lethality ( J:127108 )

nervous system

seizures ( J:127108 )

abnormal brain morphology ( J:127108 )

• brain cellularity is reduced particularly in the cortex and thalamus

• the cerebellum and nuclei of the pons and medulla exhibit lose of cellularity that is associated with abundant pyknotic cells

• apoptotic cells are observed in the thalamus, dendate gyrus of the hippocampus and cerebellum

decreased brain size ( J:127108 )

abnormal neuron morphology ( J:127108 )

• large neurons are surrounded by ameboid-shaped cells (microglia-like) and those in the motor trigeminal nuclei and pons regions have huge vacuoles likely due to lipid accumulation

hippocampal neuron degeneration ( J:127108 )

• neurons in the CA3 and dendate gyrus undergo degeneration

• however, neurons in the CA1 are unaffected

decreased cerebral cortex pyramidal cell number ( J:127108 )

• pyramidal neurons are lost from the cortical layer

decreased Purkinje cell number ( J:127108 )

• the number of Purkinje cells in the cerebellum is decreased compared to in wild-type mice and those present exhibit a profound swelling in their axons

behavior/neurological

abnormal gait ( J:127108 )

• mice develop a rapidly progressing neurological disease beginning at day 10 with abnormal gait, hyperextension of the neck and seizure

paralysis ( J:127108 )

• at 2 weeks of age mice develop end-stage paralysis

seizures ( J:127108 )

hematopoietic system

abnormal macrophage morphology ( J:127108 )

• visceral Gaucher cells (macrophages with lipid accumulation observed in Gaucher disease) are present in the spleen and liver

homeostasis/metabolism

abnormal lipid homeostasis ( J:127108 )

• glucosylceramide accumulates in the brain, spleen and liver unlike in wild-type mice

immune system

abnormal macrophage morphology ( J:127108 )

• visceral Gaucher cells (macrophages with lipid accumulation observed in Gaucher disease) are present in the spleen and liver

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Gaucher's disease type II		DOID:0110958	OMIM:230900	J:127108