Phenotypes associated with this allele

• Allele Symbol: Ctf1^tm1Msd
• Allele Name: targeted mutation 1, Michael Sendtner
• Allele ID: MGI:2675769
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ctf1^tm1Msd/Ctf1^tm1Msd	B6.Cg-Ctf1^tm1Msd	MGI:5294956
hm2	Ctf1^tm1Msd/Ctf1^tm1Msd	involves: 129S2/SvPas * C57BL/6	MGI:2675784

Genotype
MGI:5294956

hm1

• Allelic Composition: Ctf1^tm1Msd/Ctf1^tm1Msd
• Genetic Background: B6.Cg-Ctf1^tm1Msd

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

growth/size/body

obese ( J:176727 )

• mutants develop spontaneous adult-onset obesity, with weight gain first seen starting at 6 months of age

increased susceptibility to diet-induced obesity ( J:176727 )

• 2 month old mutants fed a high-fat diet for 12 weeks gain more weight and accumulate more epididymal, retroperitoneal, and subcutaneous fat mass than wild-type mice

adipose tissue

increased total body fat amount ( J:176727 )

• weight gain is mostly due to increased adipose tissue

decreased fat cell mitochondrial DNA content ( J:176727 )

• mitochondrial DNA levels are reduced in white adipose tissue, indicating impaired mitochondrial biogenesis

increased fat cell size ( J:176727 )

• adipocyte hypertrophy is seen in mature mutants

behavior/neurological

decreased food intake ( J:176727 )

• mutants become obese despite reduced food intake from 2-12 months compared to controls

homeostasis/metabolism

hyperglycemia ( J:176727 )

• hyperglycemia is seen from 6 months of age

increased circulating insulin level ( J:176727 )

• hyperinsulinemia is seen from 6 months of age

increased circulating leptin level ( J:176727 )

• increase in serum leptin levels in parallel with progression of weight gain

increased circulating cholesterol level ( J:176727 )

• hypercholesterolemia is seen from 6 months of age

decreased circulating free fatty acids level ( J:176727 )

• old obese mutants exhibit lower circulating free fatty acids than controls

decreased energy expenditure ( J:176727 )

• in 2 month old mutants, energy expenditure is reduced compared to wild-type mice, with differences increasing with age

increased susceptibility to diet-induced obesity ( J:176727 )

• 2 month old mutants fed a high-fat diet for 12 weeks gain more weight and accumulate more epididymal, retroperitoneal, and subcutaneous fat mass than wild-type mice

decreased oxygen consumption ( J:176727 )

• in 2 month old mutants, oxygen consumption is reduced compared to wild-type mice, with differences increasing with age

increased respiratory quotient ( J:176727 )

• respiratory quotient is elevated in mature obese mutants compared to mature wild-type mice

insulin resistance ( J:176727 )

• insulin resistance is seen in obese mutants

enhanced lipolysis ( J:176727 )

• adipocytes from obese mutants show increased baseline lipolysis and respond poorly to isoproterenol

endocrine/exocrine glands

increased pancreatic islet number ( J:176727 )

• pancreatic islet number is increased at 9 and 12 months of age

enlarged pancreatic islets ( J:176727 )

• pancreatic islet size is increased at 9 and 12 months of age

cellular

decreased fat cell mitochondrial DNA content ( J:176727 )

• mitochondrial DNA levels are reduced in white adipose tissue, indicating impaired mitochondrial biogenesis

abnormal aerobic respiration ( J:176727 )

• oxygen consumption is reduced in adipocytes from obese mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
abdominal obesity-metabolic syndrome		DOID:0060611	OMIM:PS605552	J:176727
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:176727

Genotype
MGI:2675784

hm2

• Allelic Composition: Ctf1^tm1Msd/Ctf1^tm1Msd
• Genetic Background: involves: 129S2/SvPas * C57BL/6

nervous system

motor neuron degeneration ( J:77294 )

• in the lumbar spinal cord, motoneuron loss is increased by 23% and 26% at P1 and P9, respectively

• in the thoracic spinal cord, motoneuron loss is increased by 29% and 43% at P1 and P9, respectively

• in the brachial spinal cord, motoneuron loss is increased by 30% and 40% at P1 and P9, respectively

• in the brainstem nuclei, facial motorneuron loss is increased by 24% and 22% at P1 and P9, respectively, by 20% at 4 weeks, and by 16% and 17% at 3 and 6 months, respectively, while hypoglossal motorneuron loss is increased by 23% at both P1 and P9

• however, no significant differences in motoneuron numbers are detected in the lumbar spinal cord at E13.5-E14.5 or in the facial nucleus at E15 relative to wild-type mice

• in addition, axotomized homozygotes show no significant further loss of motorneurons in the facial nucleus at 2 or 6 months relative to wild-type mice

behavior/neurological

decreased grip strength ( J:77294 )

• at 4 months of age, homozygotes display a significant reduction in grip strength relative to wild-type littermates

• however, loss of muscle strength does not result in any other obvious behavioral deficits