Phenotypes associated with this allele

• Allele Symbol: Dbt^tm1Geh
• Allele Name: targeted mutation 1, Gregg E Homanics
• Allele ID: MGI:3704091
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dbt^tm1Geh/Dbt^tm1Geh	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3704912
cx2	Dbt^tm1Geh/Dbt^tm1Geh Tg(tetO-DBT)A1Geh/0 Tg(Cebpb-tTA)5Bjd/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB * NMRI	MGI:3704913
cx3	Dbt^tm1Geh/Dbt^tm1Geh Tg(tetO-DBT)525AGeh/0 Tg(Cebpb-tTA)5Bjd/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB * NMRI	MGI:3704920

Genotype
MGI:3704912

hm1

• Allelic Composition: Dbt^tm1Geh/Dbt^tm1Geh
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

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

mortality/aging

postnatal lethality, complete penetrance ( J:119973 )

• on day 1 after birth, homozygotes become moribund and almost all die within 72 hours of birth; one pup lived to P13

behavior/neurological

lethargy ( J:119973 )

• on first day after birth, homozygotes become lethargic

homeostasis/metabolism

abnormal circulating amino acid level ( J:119973 )

• homozygotes have nearly 3-fold increased levels of branched-chain amino acids (BCAA, sum of leucine + isoleucine + valine) in the blood compared to wild-type littermates

• BCAA/alanine ratio is 6-fold higher than in wild-type or heterozygotes

decreased circulating alanine level ( J:119973 )

• blood levels of alanine are markedly lower than in wild-type or heterozygous mice

decreased circulating glutamic acid level ( J:119973 )

• blood levels of glutamate are markedly lower than in wild-type or heterozygous mice

decreased circulating glutamine level ( J:119973 )

• blood levels of glutamine are markedly lower than in wild-type or heterozygous mice

aminoaciduria ( J:119973 )

• homozygotes have nearly 3-fold increased levels of BCAA in urine compared to wild-type littermates

respiratory system

respiratory distress ( J:119973 )

• on first day after birth, homozygotes display gasping

renal/urinary system

aminoaciduria ( J:119973 )

• homozygotes have nearly 3-fold increased levels of BCAA in urine compared to wild-type littermates

integument

pallor ( J:119973 )

• on first day after birth, homozygotes are pale

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maple syrup urine disease		DOID:9269	OMIM:246900 OMIM:248600 OMIM:615135	J:119973

Genotype
MGI:3704913

cx2

• Allelic Composition: Dbt^tm1Geh/Dbt^tm1Geh; Tg(tetO-DBT)A1Geh/0; Tg(Cebpb-tTA)5Bjd/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB * NMRI

mortality/aging

premature death ( J:119973 )

• transgenic mice survival is only ~16 weeks, when mice become moribund and are sacrificed

postnatal lethality ( J:119973 )

• approximately 4% of pups surviving to weaning have this genotype, compared to a theoretical survival rate or 14%, indicating partial rescue of the Dbt^tm1Geh phenotype

homeostasis/metabolism

abnormal circulating amino acid level ( J:119973 )

• blood levels of alanine, glutamate, and glutamine are reduced compared to controls, but greater than in Dbt^tm1Geh homozygous mice

• BCAA/alanine (BCAA -branched-chain amino acids - leucine + isoleucine + valine) values are intermediate between controls and Dbt-null mice between 4-7 weeks of age

abnormal enzyme/coenzyme activity ( J:119973 )

• levels of branched-chain keto acid dehydrogenase (BCKDH) activity are only 5-6% of controls levels, despite nearly equal protein levels, indicating suboptimal BCKDH activity of protein assembled with human E2

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maple syrup urine disease		DOID:9269	OMIM:246900 OMIM:248600 OMIM:615135	J:119973

Genotype
MGI:3704920

cx3

• Allelic Composition: Dbt^tm1Geh/Dbt^tm1Geh; Tg(tetO-DBT)525AGeh/0; Tg(Cebpb-tTA)5Bjd/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB * NMRI

mortality/aging

premature death ( J:119973 )

• only 12% (2/16) transgenic mice survive to 20 weeks; two surviving mice live to 40 and 60 weeks, respectively

postnatal lethality ( J:119973 )

• approximately 11% of pups surviving to weaning have this genotype, compared to a theoretical survival rate or 14%, indicating high degree of rescue of the Dbt-deficient phenotype

homeostasis/metabolism

abnormal circulating amino acid level ( J:119973 )

• blood levels of glutamate are reduced compared to controls, but greater than in Dbt^tm1Geh homozygotes

• BCAA/alanine (BCAA -branched-chain amino acids - leucine + isoleucine + valine) values are intermediate between controls and Dbt^tm1Geh homozygotes between 4-10 weeks of age

abnormal enzyme/coenzyme activity ( J:119973 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maple syrup urine disease		DOID:9269	OMIM:246900 OMIM:248600 OMIM:615135	J:119973