Phenotypes associated with this allele

• Allele Symbol: Gnao1^tm1Lbi
• Allele Name: targeted mutation 1, Lutz Birnbaumer
• Allele ID: MGI:2152685
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gnao1^tm1Lbi/Gnao1^tm1Lbi	involves: 129S7/SvEvBrd * C57BL/6J	MGI:3615485

Genotype
MGI:3615485

hm1

• Allelic Composition: Gnao1^tm1Lbi/Gnao1^tm1Lbi
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

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

mortality/aging

premature death ( J:46898 )

• 50% of homozygotes die of unknown reasons by 7 weeks; only 2 of 31 homozygotes survive beyond 50 weeks

preweaning lethality, incomplete penetrance ( J:46898 )

• at weaning, homozygotes are obtained at a reduced Mendelian frequency (7% vs expected 25%)

behavior/neurological

tremors ( J:46898 )

• homozygotes exhibit a generalized tremor

impaired coordination ( J:46898 )

• homozygotes display impaired motor control, falling from rotarods and 1-inch wide beams

hyperactivity ( J:46898 )

• homozygotes appear to move continuously

unidirectional circling ( J:46898 )

• homozygotes exhibit an extreme turning behavior that has them running in circles at varying speeds for hours on end, both in cages and in open-field tests

• nearly all homozygotes turn only counterclockwise

hyperalgesia ( J:46898 )

• homozygotes are hyperalgesic in the hot plate test (55 C)

decreased thermal nociceptive threshold ( J:46898 )

• homozygotes exhibit a significantly reduced latency time in the hot plate test, as measured by front paw licking and rear paw shaking

abnormal social investigation ( J:46898 )

• homozygotes interact with littermates in a friendly but hasty manner

nervous system

abnormal channel response ( J:46898 )

• similar to wild-type, mutant sensory dorsal root ganglion (DRG) cells show absence of prepulse potentiation before agonist addition, indicating lack of accumulation of an unbalanced excess of functionally active beta/gamma dimers in mutant DRGs

• however, mutant DRG cells display a partial (30%) reduction in opioid-receptor-mediated inhibition of neuronal Ca²⁺ channel currents; in contrast, inhibition of cardiac adenylyl cyclase by carbachol (50-55% at saturation) remains unaffected

• in addition, 25% of mutant DRG cells exhibit a shift in the position of the conductance-voltage relationship, with Ca²⁺ channel currents activated at voltages that are 13.3 1.7 mV lower than in wild-type DRG cells

growth/size/body

decreased body size ( J:46898 )

• at 3 weeks, homozygotes are smaller than wild-type littermates

decreased body weight ( J:46898 )

• at 3 weeks, the mean body weight of homozygotes is only 45% the weight of wild-type mice

• however, surviving homozygotes grow well and exhibit a normal body weight by 8 weeks

• weaned homozygotes fail to feed well by themselves in standard cages either because of the small size or because of general weakness but they eat food supplied as a paste on a dish `

reproductive system

infertility ( J:46898 )

• neither female nor male homozygotes mate successfully