Phenotypes associated with this allele

• Allele Symbol: Gba^tm1.1Karl
• Allele Name: targeted mutation 1.1, Stefan Karlsson
• Allele ID: MGI:3687966
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gba^tm1.1Karl/Gba^tm1.1Karl	involves: 129S1/Sv * 129X1/SvJ	MGI:3688419
ht2	Gba^tm1.1Karl/Gba^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3688421
cn3	Gba^tm1Karl/Gba^tm1.1Karl Tg(Mx1-cre)1Cgn/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:3688418

Genotype
MGI:3688419

hm1

• Allelic Composition: Gba^tm1.1Karl/Gba^tm1.1Karl
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

mortality/aging

neonatal lethality, complete penetrance ( J:113751 )

• mice die within first day of life from lethal skin phenotype

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Gaucher's disease type I		DOID:0110957	OMIM:230800	J:113751

Genotype
MGI:3688421

ht2

• Allelic Composition: Gba^tm1.1Karl/Gba⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:113751 )

• mice have ~50% glucosylceramidase activity of wild-type

Genotype
MGI:3688418

cn3

• Allelic Composition: Gba^tm1Karl/Gba^tm1.1Karl; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

growth/size/body

enlarged liver ( J:113751 )

• after 16 months of disease (cre) induction, liver is slightly enlarged, but less so than spleen

enlarged spleen ( J:113751 )

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:113751 )

• 5 months post-transplant of wild-type bone marrow into deficient mice 1.5 months after Gba-depletion results in significantly higher glucosylceramidase activity in bone marrow, spleen and liver of recipients

hematopoietic system

decreased hematocrit ( J:113751 )

• after 16 months of disease (cre) induction, significantly reduced compared to control

decreased hemoglobin content ( J:113751 )

• after 16 months of disease (cre) induction, significantly reduced compared to control

decreased mean corpuscular volume ( J:113751 )

• after 16 months of disease (cre) induction, significantly reduced compared to control

abnormal spleen morphology ( J:113751 )

• after disease (cre) induction following birth, 12 month -old Gba-deficient mice have disrupted splenic architecture

enlarged spleen ( J:113751 )

intermingled spleen red and white pulp ( J:113751 )

• demarcation of red and white pulp is not evident

immune system

abnormal immune system organ morphology ( J:113751 )

• spleen, thymus, liver and lymph nodes of 12 month old cre-induced Gba-null mice show massive infiltration of mainly multinucleated Gaucher cells, and cytoplasm had "wrinkled tissue-paper"-like appearance

abnormal spleen morphology ( J:113751 )

• after disease (cre) induction following birth, 12 month -old Gba-deficient mice have disrupted splenic architecture

enlarged spleen ( J:113751 )

intermingled spleen red and white pulp ( J:113751 )

• demarcation of red and white pulp is not evident

abnormal response to transplant ( J:113751 )

• 5 months after bone marrow transplant, no Gaucher cells are observed

• if Gaucher disease is allowed to progress for 7.5 months before bone marrow transplant, when examined at 13 months of age, recipients have been cleared of all (4/6) or all but a few (2/6) Gaucher cells

liver/biliary system

enlarged liver ( J:113751 )

• after 16 months of disease (cre) induction, liver is slightly enlarged, but less so than spleen

pale liver ( J:113751 )

• after 16 months of disease (cre) induction, liver is pale

skeleton

abnormal bone marrow morphology ( J:113751 )

• bone marrow shows massive infiltration by Gaucher cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Gaucher's disease type I		DOID:0110957	OMIM:230800	J:113751