Phenotypes associated with this allele

• Allele Symbol: Ppp1r3a^tm1Ptwc
• Allele Name: targeted mutation 1, Patricia T W Cohen
• Allele ID: MGI:2653915
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ppp1r3a^tm1Ptwc/Ppp1r3a^tm1Ptwc	involves: 129P2/OlaHsd * C57BL/6J	MGI:2653988

Genotype
MGI:2653988

hm1

• Allelic Composition: Ppp1r3a^tm1Ptwc/Ppp1r3a^tm1Ptwc
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

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

growth/size/body

increased body weight ( J:82422 )

• at >12 months of age, homozygotes of both sexes weigh ~20% more than wild-type controls

obese ( J:82422 )

• at >12 months of age, homozygotes are obese

increased body length ( J:82422 )

• at >12 months of age, homozygotes show a small increase in body length relative to wild-type controls

increased susceptibility to weight gain ( J:82422 )

• at >3 months of age, both male and female homozygotes gain weight more rapidly than wild-type controls

adipose tissue

increased abdominal adipose tissue amount ( J:82422 )

• at >12 months of age, homozygotes show a ~4-fold increase in abdominal adipose tissue relative to wild-type controls

increased total body fat amount ( J:82422 )

• at >12 months of age, homozygotes of both sexes display increased fat deposits around the heart and massive deposits of abdominal fat

• increased fat deposition is likely to be due to impaired blood glucose utilization in skeletal muscle

homeostasis/metabolism

impaired glucose tolerance ( J:82422 )

• at 11 months, of age, fasted homozygotes of both sexes exhibit ~40% higher blood glucose levels at all times tested after a glucose challenge relative to similarly treated wild-type controls, and blood glucose returns to baseline levels at a much slower rate than in wild-type controls

• however, at 11 months of age, homozygotes of both sexes display normal fasting blood glucose levels relative to wild-type controls

• neither male nor female homozygotes display glucose intolerance at 6-8 months of age

decreased skeletal muscle glycogen level ( J:82422 )

• after a 16-hr overnight fast, glycogen levels in skeletal muscle are reduced to ~10% of wild-type controls

insulin resistance ( J:82422 )

• at >11 months of age, homozygotes develop insulin resistance in skeletal muscle

abnormal enzyme/coenzyme activity ( J:82422 )

• basal glycogen synthase (GS) activity, presented as a ratio of GS activity in the absence of G-6P divided by the total activity in the presence of G-6P, is equal to only 0.1 in mutant skeletal muscle relative to 0.3 in wild-type controls

• insulin-stimulated GS activity in mutant skeletal muscle is increased by 1.5- to 2-fold, but fails to even approach the basal levels observed in wild-type controls, rising only to 0.2

• both basal and insulin-stimulated phopshorylase activity, presented as a ratio of phosphorylase activity in the absence of AMP divided by the total activity in the presence of AMP, is increased in mutant skeletal muscle relative to wild-type controls

• total levels of both phosphorylase and GS activity are reduced by 40-50% in mutant skeletal muscle relative to wild-type controls

• basal activity of PP1-R5/PTG, another glycogen targeted form of protein phosphatase 1 (PP1), is decreased in mutant skeletal muscle relative to that in wild-type controls

• insulin-stimulated PP1-R5/PTG activity is doubled in mutant skeletal muscle but not significantly altered in wild-type skeletal muscle

muscle

decreased skeletal muscle cell glucose uptake ( J:82422 )

• at >12 months of age, basal uptake of 2-deoxy-d-[1,2-3H]-glucose (2-DOG) into skeletal muscle is reduced by 69% relative to wild-type controls during a glucose tolerance test

• in contrast, glucose transport into adipose tissue, glycogen levels, and glycogen synthase activity in adipose tissue remain normal

decreased skeletal muscle glycogen level ( J:82422 )

• after a 16-hr overnight fast, glycogen levels in skeletal muscle are reduced to ~10% of wild-type controls

cellular

decreased skeletal muscle cell glucose uptake ( J:82422 )

• at >12 months of age, basal uptake of 2-deoxy-d-[1,2-3H]-glucose (2-DOG) into skeletal muscle is reduced by 69% relative to wild-type controls during a glucose tolerance test

• in contrast, glucose transport into adipose tissue, glycogen levels, and glycogen synthase activity in adipose tissue remain normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:82422