Phenotypes associated with this allele

• Allele Symbol: Rai1^tm1Jrl
• Allele Name: targeted mutation 1, James R Lupski
• Allele ID: MGI:3526160
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rai1^tm1Jrl/Rai1^tm1Jrl	involves: 129S/SvEvBrd * C57BL/6	MGI:3577936
ht2	Rai1^tm1Jrl/Rai1^+	B6.129S7-Rai1^tm1Jrl/J	MGI:4835032
ht3	Rai1^tm1Jrl/Rai1^+	involves: 129S/SvEvBrd * C57BL/6	MGI:3577939
cx4	Dp(11Cops3-Rnf112)1Jrl/0 Rai1^tm1Jrl/Rai1^+	involves: 129S/SvEvBrd * 129S7/SvEvBrd * C57BL/6	MGI:3758727

Genotype
MGI:3577936

hm1

• Allelic Composition: Rai1^tm1Jrl/Rai1^tm1Jrl
• Genetic Background: involves: 129S/SvEvBrd * C57BL/6

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

mortality/aging

decreased survivor rate ( J:98073 )

• 1 mouse survived past 3 months

lethality throughout fetal growth and development, incomplete penetrance ( J:98073 )

• very few survive to E15.5-E18.5 (2 in 60 embryos)

• relatively few born (4.5%)

postnatal lethality, incomplete penetrance ( J:98073 )

• 6 of 13 mice born alive died within a few days of birth

• 6 of 13 mice born alive died around weaning

• 1 survived past 3 months

embryonic lethality between implantation and somite formation, incomplete penetrance ( J:98073 )

• at E7.5, 16.5% of embryo were live homozygotes, an additional 7.4% of embryos were dead homozygotes

• implantation was normal with death occurring during gastrulation and organogenesis

growth/size/body

malocclusion ( J:98073 )

• sometimes upper and lower incisors are misaligned

abnormal nasal bone morphology ( J:98073 )

• sometimes curved to right or left

broad nasal bone ( J:98073 )

short nasal bone ( J:98073 )

abnormal snout morphology ( J:98073 )

• lateral bending of snout with and without misalignment of incisors

short snout ( J:98073 )

postnatal growth retardation ( J:98073 )

• grossly normal at birth but severely growth retarded thereafter

craniofacial

malocclusion ( J:98073 )

• sometimes upper and lower incisors are misaligned

abnormal nasal bone morphology ( J:98073 )

• sometimes curved to right or left

broad nasal bone ( J:98073 )

short nasal bone ( J:98073 )

abnormal snout morphology ( J:98073 )

• lateral bending of snout with and without misalignment of incisors

short snout ( J:98073 )

skeleton

polyphalangy ( J:98073 )

• extra cartilage seen in digit 5

abnormal axial skeleton morphology ( J:98073 )

malocclusion ( J:98073 )

• sometimes upper and lower incisors are misaligned

abnormal nasal bone morphology ( J:98073 )

• sometimes curved to right or left

broad nasal bone ( J:98073 )

short nasal bone ( J:98073 )

abnormal thyroid cartilage morphology ( J:98073 )

• hypoplastic thyroid bones with central elements unformed

abnormal rib development ( J:98073 )

• 13th rib is thinner than normal and fails to articulate with vertebral body

abnormal thoracic vertebrae morphology ( J:98073 )

• dorsal arches of some thoracic vertebrae failed to close

• T2 lacked spinal processes

kyphosis ( J:125089 )

• 10% of mice over 4 months of age display kyphosis

abnormal cervical vertebrae morphology ( J:98073 )

• restricted head rotation

• failure of some dorsal arches to close

• C4, C5, C6 transverse foramina failed to close

fusion of atlas and odontoid process ( J:98073 )

• odontoid process fused to atlas

abnormal vertebral arch development ( J:98073 )

• failure of some cervical and thoracic dorsal arches to close

• C4, C5, C6 transverse foramina failed to close

• dorsal arches of some thoracic vertebrae failed to close

limbs/digits/tail

polyphalangy ( J:98073 )

• extra cartilage seen in digit 5

respiratory system

abnormal nasal bone morphology ( J:98073 )

• sometimes curved to right or left

broad nasal bone ( J:98073 )

short nasal bone ( J:98073 )

abnormal thyroid cartilage morphology ( J:98073 )

• hypoplastic thyroid bones with central elements unformed

behavior/neurological

abnormal contextual conditioning behavior ( J:125089 )

• mice display defective context-dependent learning relative to wild-type mice

abnormal cued conditioning behavior ( J:125089 )

• mice display defective cued (tone) conditioned learning relative to wild-type mice

increased anxiety-related response ( J:125089 )

• in a light-dark test, mice display increased latency to enter the light relative to wild-type mice

limb grasping ( J:125089 )

• when suspended by their tails, mice display hindlimb, and occasionally hind- and forelimb, clasping even after three months of age whereas wild-type mice hold their legs apart

impaired coordination ( J:125089 )

• when placed on a vertical pole, mice fall off more frequently and more readily as compared to wild-type mice

• in a wire suspension test, mice fall off after 30 seconds compared to 60 seconds for heterozygotes

• when placed on a thin rod, mice fall off after 11 seconds compared to 60 seconds for wild-type mice

seizures ( J:125089 )

• seizures are observed after 3 months of age

• sudden behavioral arrest correlates with electrographic seizures

tonic-clonic seizures ( J:125089 )

nervous system

seizures ( J:125089 )

• seizures are observed after 3 months of age

• sudden behavioral arrest correlates with electrographic seizures

tonic-clonic seizures ( J:125089 )

abnormal brain wave pattern ( J:125089 )

• video electroencephalogram indicates abnormal wake and sleep background punctuated by generalized spikes, multiple spikes and sharp waves

• sudden behavioral arrest correlates with electrographic seizures

Genotype
MGI:4835032

ht2

• Allelic Composition: Rai1^tm1Jrl/Rai1⁺
• Genetic Background: B6.129S7-Rai1^tm1Jrl/J

endocrine/exocrine glands

increased amylin secretion ( J:164451 )

• increase in serum amylin levels in fasted mice older than 30 weeks of age

growth/size/body

obese ( J:164451 )

• although at 5 weeks of age, males are smaller than wild-type, by 10 and 15 weeks of age, no weight differences are seen between mutants and wild-type, and by 20 weeks of age, males are significantly larger than wild-type males

• females begin to gain weight around 20 weeks of age and are significantly larger at 25 and 30 weeks of age

• rate of weight gain in about 2-fold that of wild-type

• mice do not exhibit ketonuria or differences in insulin or glucose levels

adipose tissue

increased white adipose tissue amount ( J:164451 )

♀ • increase in white adipose tissue in females, with substantial adipose tissue found in thoracic cavity of older females and substantial fat stores around abdominal organs

increased abdominal adipose tissue amount ( J:164451 )

♀ • females have a higher proportion of abdominal fat than wild-type mice

♀ • however no differences in adipocyte cell size or shape are observed

behavior/neurological

increased food intake ( J:164451 )

• fasting studies show a delayed satiation response compared to wild-type mice; mutants continue to eat larger amounts even 60 hours after fasting when wild-type return to normal levels of eating

polyphagia ( J:164451 )

• mutants are hyperphagic at 20 and 25 weeks, consuming about 50% more food than wild-type

• at 15 weeks of age, mice consume more food even though their weight is no different from wild-type

• at 15 weeks of age, mice consume a higher proportion of their food during the light phase (rest phase) than wild-type mice

abnormal circadian behavior ( J:164451 )

• at 15 weeks of age, mice consume a higher proportion of their food during the light phase (rest phase) than wild-type mice

homeostasis/metabolism

increased circulating corticosterone level ( J:164451 )

• corticosterone levels are higher in fasted mutants than in wild-type mice

increased circulating leptin level ( J:164451 )

• increase in serum leptin levels in fasted mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Smith-Magenis syndrome		DOID:0060768	OMIM:182290	J:164451

Genotype
MGI:3577939

ht3

• Allelic Composition: Rai1^tm1Jrl/Rai1⁺
• Genetic Background: involves: 129S/SvEvBrd * C57BL/6

growth/size/body

abnormal nasal bone morphology ( J:98073 )

• main cause of craniofacial defects

broad nasal bone ( J:98073 )

short nasal bone ( J:98073 )

abnormal snout morphology ( J:98073 )

• concave shape to snout

• right or left curvature of snout (7% of animals)

broad snout ( J:98073 )

• short, broad snouts seen in about 18% of animals

short snout ( J:98073 )

• short, broad snouts seen in about 18% of animals

decreased body weight ( J:98073 )

• underweight at 4-7 weeks of age

obese ( J:98073 )

• males become overweight by 20 weeks of age

• females overweight by 23 weeks of age

postnatal growth retardation ( J:125089 )

• mice exhibit postnatal growth retardation relative to wild-type mice

• however, by 3 months there is no significant differences in weight relative to wild-type mice

craniofacial

abnormal nasal bone morphology ( J:98073 )

• main cause of craniofacial defects

broad nasal bone ( J:98073 )

short nasal bone ( J:98073 )

abnormal snout morphology ( J:98073 )

• concave shape to snout

• right or left curvature of snout (7% of animals)

broad snout ( J:98073 )

• short, broad snouts seen in about 18% of animals

short snout ( J:98073 )

• short, broad snouts seen in about 18% of animals

skeleton

abnormal nasal bone morphology ( J:98073 )

• main cause of craniofacial defects

broad nasal bone ( J:98073 )

short nasal bone ( J:98073 )

behavior/neurological

increased vertical activity ( J:125089 )

• in an open field, mice rear more than wild-type mice

seizures ( J:125089 )

• 2% of mice display seizures after the age of 4 months

nervous system

seizures ( J:125089 )

• 2% of mice display seizures after the age of 4 months

abnormal brain wave pattern ( J:125089 )

• video electroencephalogram indicates abnormal wake and sleep background with frequent epileptiform discharges despite the lack of electographic seizures

respiratory system

abnormal nasal bone morphology ( J:98073 )

• main cause of craniofacial defects

broad nasal bone ( J:98073 )

short nasal bone ( J:98073 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Smith-Magenis syndrome		DOID:0060768	OMIM:182290	J:98073

Genotype
MGI:3758727

cx4

• Allelic Composition: Dp(11Cops3-Rnf112)1Jrl/0; Rai1^tm1Jrl/Rai1⁺
• Genetic Background: involves: 129S/SvEvBrd * 129S7/SvEvBrd * C57BL/6

behavior/neurological

hyperactivity ( J:114996 )

• mice are more active than wild-type mice

• however, anxiety and defective learning and memory behaviors observed in either heterozygote are no longer present

growth/size/body

growth/size/body region phenotype ( J:114996 )

N • mice have normal body weights unlike in either heterozygote

nervous system

nervous system phenotype ( J:114996 )

N • unlike in Rai1^tm1Jrl heterozygotes, there is no evidence of epileptic seizures