Phenotypes associated with this allele

• Allele Symbol: Alk^tm2.1Ics
• Allele Name: targeted mutation 2.1, Mouse Clinical Institute
• Allele ID: MGI:5705326
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Alk^tm2.1Ics/Alk^tm2.1Ics	B6N.129S2(Cg)-Alk^tm2.1Ics	MGI:5789379
hm2	Alk^tm2.1Ics/Alk^tm2.1Ics	involves: 129S2/SvPas * C57BL/6	MGI:5789373
ht3	Alk^tm2.1Ics/Alk^+	B6N.129S2(Cg)-Alk^tm2.1Ics	MGI:5789378
ht4	Alk^tm2.1Ics/Alk^+	involves: 129S2/SvPas * C57BL/6	MGI:5789372
cx5	Alk^tm2.1Ics/? Tg(Th-MYCN)41Waw/0	involves: 129S2/SvPas * 129X1/SvJ * BALB/c * C57BL/6 * C57BL/6J	MGI:5789376

Genotype
MGI:5789379

hm1

• Allelic Composition: Alk^tm2.1Ics/Alk^tm2.1Ics
• Genetic Background: B6N.129S2(Cg)-Alk^tm2.1Ics

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

mortality/aging

neonatal lethality, incomplete penetrance ( J:226655 )

• a peak of lethality is seen between 24 hours (P1) and 48 hours (P2) after birth

postnatal lethality, incomplete penetrance ( J:226655 )

• a peak of lethality is seen between 24 hours (P1) and 48 hours (P2) after birth

behavior/neurological

abnormal behavior ( J:226655 )

• the movement response to hypercapnia is disrupted

decreased food intake ( J:226655 )

• only 13% of mutant newborns have a full stomach compared to 61% of wild-type mice, indicating reduced milk intake

growth/size/body

decreased body size ( J:226655 )

• mice that survive more than 2 days are smaller

decreased body weight ( J:226655 )

• mice that survive more than 2 days are lighter

integument

delayed hair appearance ( J:226655 )

• mice that survive more than 2 days show a delay in fur growth

delayed skin pigmentation appearance ( J:226655 )

• mice that survive more than 2 days present with a delay in skin pigmentation

respiratory system

apnea ( J:226655 )

• mice spend about 30% more time in apneas in normoxia condition

• however, mice breathe correctly with the same rate and volume compared to controls and respond normally to hypercapnia and hypoxia

skeleton

abnormal long bone diaphysis morphology ( J:226655 )

• surviving mice exhibit shorter femoral and tibial diaphysis

pigmentation

delayed skin pigmentation appearance ( J:226655 )

• mice that survive more than 2 days present with a delay in skin pigmentation

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:226655 )

N • mice exhibit normal adrenal glands at birth

nervous system

nervous system phenotype ( J:226655 )

N • mice do not exhibit abnormalities in brainstem histology at birth

Genotype
MGI:5789373

hm2

• Allelic Composition: Alk^tm2.1Ics/Alk^tm2.1Ics
• Genetic Background: involves: 129S2/SvPas * C57BL/6

nervous system

abnormal sympathetic ganglion morphology ( J:228124 )

• excess of proliferation in sympathetic ganglia

abnormal stellate ganglion morphology ( J:228124 )

• increase in size of the stellate ganglia in adults and at birth

• increase in the number of neuroblasts in the stellate ganglia at E12.5, with a further increase at E14.5

abnormal superior cervical ganglion morphology ( J:228124 )

• increase in the number of neuroblasts in the superior cervical ganglia at E12.5, with a further increase at E14.5

enlarged superior cervical ganglion ( J:228124 )

• increase in size of the superior cervical ganglia in adults and at birth

Genotype
MGI:5789378

ht3

• Allelic Composition: Alk^tm2.1Ics/Alk⁺
• Genetic Background: B6N.129S2(Cg)-Alk^tm2.1Ics

behavior/neurological

abnormal behavior ( J:226655 )

♂ • the movement response to hypercapnia is disrupted

♂ • however, mice do not show differences in the Y-maze or the tail suspension tests

decreased food intake ( J:226655 )

♂ • 48% of newborn mutants have a full stomach compared to 61% of wild-type mice, indicating some reduction in milk intake

increased anxiety-related response ( J:226655 )

♂ • during the dark/light test, mice spend less time in the light side, wait longer before going for the first time in the light side and do less light/dark transitions

increased grip strength ( J:226655 )

♂ • mice show increased muscle strength when allowed to grip with all paws

decreased vertical activity ( J:226655 )

♂ • mice exhibit less rears during the dark phase

decreased locomotor activity ( J:226655 )

♂ • mice exhibit less locomotor activity during the dark phase

homeostasis/metabolism

increased circulating alkaline phosphatase level ( J:226655 )

♂ • slightly higher levels

increased circulating chloride level ( J:226655 )

♂ • slightly higher levels

vision/eye

abnormal eye morphology ( J:226655 )

♂ • 7 of 11 mice exhibit minor abnormalities of the visual system, showing a small zone of higher reflectance under one of the main blood vessels and/or a small white spot under a vein

Genotype
MGI:5789372

ht4

• Allelic Composition: Alk^tm2.1Ics/Alk⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

nervous system

abnormal sympathetic ganglion morphology ( J:228124 )

• excess of proliferation in sympathetic ganglia

abnormal stellate ganglion morphology ( J:228124 )

• increase in size of the stellate ganglia in adults and at birth

• increase in the number of neuroblasts per ganglion in the stellate ganglia at E14.5

abnormal superior cervical ganglion morphology ( J:228124 )

• increase in the number of neuroblasts per ganglion in the superior cervical ganglia at E14.5

enlarged superior cervical ganglion ( J:228124 )

• increase in size of the superior cervical ganglia in adults and at birth

Genotype
MGI:5789376

cx5

• Allelic Composition: Alk^tm2.1Ics/?; Tg(Th-MYCN)41Waw/0
• Genetic Background: involves: 129S2/SvPas * 129X1/SvJ * BALB/c * C57BL/6 * C57BL/6J

neoplasm

increased neuroblastoma incidence ( J:228124 , J:261033 )

• tumors are classified as neuroblastoma, stroma-poor, poorly differentiated or differentiating (J:228124)

• tumor onset occurs earlier than in mice carrying the Alk^tm1.1Ics allele (J:228124)

• abdominal tumors are median, perivascular and locally invasive without evidence of macroscopic tumor spread to other organs (J:228124)

• tumors at 2 or 3 locations (abdominal/thoracic/cervical) are seen in 100% of mice (J:228124)

• mice treated with vandetanib, a kinase inhibitor, show a reduction in abdominal tumor weight (J:228124)

mortality/aging

premature death ( J:261033 )

• mice begin to die after 50 days of age, with 10% survival after 150 days of age

nervous system

increased neuroblastoma incidence ( J:228124 , J:261033 )

• tumors are classified as neuroblastoma, stroma-poor, poorly differentiated or differentiating (J:228124)

• tumor onset occurs earlier than in mice carrying the Alk^tm1.1Ics allele (J:228124)

• abdominal tumors are median, perivascular and locally invasive without evidence of macroscopic tumor spread to other organs (J:228124)

• tumors at 2 or 3 locations (abdominal/thoracic/cervical) are seen in 100% of mice (J:228124)

• mice treated with vandetanib, a kinase inhibitor, show a reduction in abdominal tumor weight (J:228124)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:228124 , J:261033