Phenotypes associated with this allele

• Allele Symbol: Irs1^Sml
• Allele Name: small
• Allele ID: MGI:3639880
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Irs1^Sml/Irs1^Sml	C3.Cg-Irs1^Sml H2^b/GrsrJ	MGI:4829466
ht2	Irs1^Sml/Irs1^+	C3.Cg-Irs1^Sml H2^b/GrsrJ	MGI:4829795

Genotype
MGI:4829466

hm1

• Allelic Composition: Irs1^Sml/Irs1^Sml
• Genetic Background: C3.Cg-Irs1^Sml H2^b/GrsrJ

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

cellular

impaired osteoblast differentiation ( J:163661 )

• in culture osteoblasts have impaired proliferation and differentiation

decreased osteoblast proliferation ( J:163661 )

• in culture osteoblasts have impaired proliferation and differentiation

growth/size/body

decreased body size ( J:163661 )

• by 2 weeks of age homozygotes are distinctly smaller and after weaning they are approximately 60% of the size by weight of heterozygotes and less than half the size by weight of wildtype controls

decreased body weight ( J:163661 )

proportional dwarf ( J:163661 )

skeleton

decreased osteoblast proliferation ( J:163661 )

• in culture osteoblasts have impaired proliferation and differentiation

abnormal femur morphology ( J:163661 )

• femur length is shortened, volumetric and areal bone mineral density are reduced, periosteal circumference and cortical thickness are reduced, trabecular number and trabecular thickness are reduced, the mineral apposition rate and bone formation rate are reduced, the minerializing surface per bone surface is less than in controls, there is a reduction in thickness of the growth plate, and there is an increase in the number of osteoclasts and osteoblasts per bone perimeter that reaches significance in females but is only suggested in males

short femur ( J:163661 )

decreased long bone epiphyseal plate size ( J:163661 )

• the growth plate of the proximal femur is markedly reduced in thickness

abnormal bone structure ( J:163661 )

impaired osteoblast differentiation ( J:163661 )

• in culture osteoblasts have impaired proliferation and differentiation

increased osteoclast cell number ( J:163661 )

• an increase in number of both osteoblasts and osteoclasts per bone perimeter in distal femurs is found in both males and females but reaches significance only in females

decreased bone mineral density ( J:163661 )

increased osteoblast cell number ( J:163661 )

• an increase in number of both osteoblasts and osteoclasts per bone perimeter in distal femurs is found in both males and females but reaches significance only in females

decreased trabecular bone thickness ( J:163661 )

• reduction in bone volume per total volume, trabecular thickness, and trabecular number is significant in both males and females but more severe in females

abnormal bone mineralization ( J:163661 )

limbs/digits/tail

abnormal femur morphology ( J:163661 )

• femur length is shortened, volumetric and areal bone mineral density are reduced, periosteal circumference and cortical thickness are reduced, trabecular number and trabecular thickness are reduced, the mineral apposition rate and bone formation rate are reduced, the minerializing surface per bone surface is less than in controls, there is a reduction in thickness of the growth plate, and there is an increase in the number of osteoclasts and osteoblasts per bone perimeter that reaches significance in females but is only suggested in males

short femur ( J:163661 )

abnormal tail morphology ( J:163661 )

• by 2 weeks of age the tail is thin and short compared with that of controls and after weaning the tail continues to have a 20% reduction in length compared with controls

short tail ( J:163661 )

thin tail ( J:163661 )

adipose tissue

decreased percent body fat/body weight ( J:163661 )

• significantly reduced percent body fat as assessed by whole body DEXA analysis at 16 weeks of age

hearing/vestibular/ear

increased or absent threshold for auditory brainstem response ( J:163661 )

• although no inner ear defects are evident, the ABR thresholds at 8, 16, and 32 kHz are significantly elevated in both male and female homozygotes assessed between 8 and 12 weeks of age

hematopoietic system

increased osteoclast cell number ( J:163661 )

• an increase in number of both osteoblasts and osteoclasts per bone perimeter in distal femurs is found in both males and females but reaches significance only in females

immune system

increased osteoclast cell number ( J:163661 )

• an increase in number of both osteoblasts and osteoclasts per bone perimeter in distal femurs is found in both males and females but reaches significance only in females

homeostasis/metabolism

decreased circulating glucose level ( J:163661 )

• fasting glucose levels are 30-40% lower than those of wild-type controls

increased circulating insulin level ( J:163661 )

• homozygotes have 3.5 to 4-fold higher circulating insulin levels and a modest increase in insulin-like growth factor 1 under fasting conditions than wild-type controls

impaired glucose tolerance ( J:163661 )

• when challenged with glucose after an overnight fast at 8 weeks of age the serum glucose levels rise as expected initially with normal kinetics but remain lower than those of wild-type controls

insulin resistance ( J:163661 )

• mild insulin resistance is revealed in non-fasting insulin tolerance tests whereing glucose levels decrease but not to the full extent seen in wild-type controls

Genotype
MGI:4829795

ht2

• Allelic Composition: Irs1^Sml/Irs1⁺
• Genetic Background: C3.Cg-Irs1^Sml H2^b/GrsrJ

growth/size/body

decreased body weight ( J:163661 )

• reduction in body weight relative to wild-type controls but less severe than in homozygotes

adipose tissue

decreased total body fat amount ( J:163661 )

• heterozygotes have less fat than wild-type controls but more than homozygotes

skeleton

abnormal femur morphology ( J:163661 )

• heterozygotes have a less severe phenotype than homozygotes with slight reduction in periosteal circumference, cortical thickness, trabecular thickness, size of the growth plate, and femur length

short femur ( J:163661 )

• slightly shorter than in wild-type controls but not shortened to the degree found in homozygotes

decreased long bone epiphyseal plate size ( J:163661 )

• the growth plate in the proximal femur is mildly reduced in size compared with wild-type controls, but not to the degree found in homozygotes

decreased bone mineral density ( J:163661 )

• intermediate phenotype between homozygotes and wild-type controls

limbs/digits/tail

abnormal femur morphology ( J:163661 )

• heterozygotes have a less severe phenotype than homozygotes with slight reduction in periosteal circumference, cortical thickness, trabecular thickness, size of the growth plate, and femur length

short femur ( J:163661 )

• slightly shorter than in wild-type controls but not shortened to the degree found in homozygotes

homeostasis/metabolism

increased circulating insulin level ( J:163661 )

• both male and female heterozygotes have an increase in fasted serum insulin that is intermediary between homozygotes and wild-type controls, and female heterozygotes, but not males, have decreased fasting serum insulin-like growth factor 1