Phenotypes associated with this allele

• Allele Symbol: Ret^tm2.1Heno
• Allele Name: targeted mutation 2.1, Hideki Enomoto
• Allele ID: MGI:3777556
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ret^tm2.1Heno/Ret^tm2.1Heno	involves: 129S/Sv * C57BL/6 * FVB/N	MGI:4820803
hm2	Ret^tm2.1Heno/Ret^tm2.1Heno	involves: C57BL/6 * FVB/N * SJL	MGI:3783340
ht3	Ret^tm2.1Heno/Ret^tm2(RET)Jmi	involves: 129S/Sv * C57BL/6 * FVB/N	MGI:4820813

Genotype
MGI:4820803

hm1

• Allelic Composition: Ret^tm2.1Heno/Ret^tm2.1Heno
• Genetic Background: involves: 129S/Sv * C57BL/6 * FVB/N

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

renal/urinary system

absent kidney ( J:135153 )

nervous system

increased neuron apoptosis ( J:135153 )

• many apoptotic figures are observed in the foregut of E10.5

abnormal enteric nervous system morphology ( J:135153 )

• no enteric nervous system precursors at E12.5

cellular

increased neuron apoptosis ( J:135153 )

• many apoptotic figures are observed in the foregut of E10.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Hirschsprung's disease		DOID:10487	OMIM:600156 OMIM:606874 OMIM:606875 OMIM:608462 OMIM:611644	J:135153

Genotype
MGI:3783340

hm2

• Allelic Composition: Ret^tm2.1Heno/Ret^tm2.1Heno
• Genetic Background: involves: C57BL/6 * FVB/N * SJL

nervous system

abnormal muscle spindle morphology ( J:132854 )

• reduced fusimotor innervation of muscle spindles

• muscle spindle innervation normal in Rectus femoris

abnormal motor neuron innervation pattern ( J:132854 )

• peroneal muscles totally lack both motor and sensory innervation in 42% of homozygotes

• 58% with normal peroneal innervation or with innervation absent only in the superficial peroneal muscles

• posterior Psoas major lacks innervation

• variable lack of innervation of Gluteus maximus, Tensor fascia latae, and Iliopsoas

decreased motor neuron number ( J:132854 )

• loss of more than 20% of motor neurons at the lumbar level

• elevated apoptosis of motor neurons between 13.5 and E15.5

muscle

abnormal hypaxial muscle morphology ( J:132854 )

abnormal gastrocnemius morphology ( J:132854 )

• reduced in size but with normal motor innervation

abnormal muscle spindle morphology ( J:132854 )

• reduced fusimotor innervation of muscle spindles

• muscle spindle innervation normal in Rectus femoris

muscular atrophy ( J:132854 )

• muscles lacking moter innervation display gross atrophy (peroneal, psoas major, tensor facia latae, etc)

limbs/digits/tail

abnormal gastrocnemius morphology ( J:132854 )

• reduced in size but with normal motor innervation

Genotype
MGI:4820813

ht3

• Allelic Composition: Ret^tm2.1Heno/Ret^tm2(RET)Jmi
• Genetic Background: involves: 129S/Sv * C57BL/6 * FVB/N

embryo

abnormal enteric neural crest cell migration ( J:135153 )

• a slight delay at E11.5 in the migratory behavior of enteric neural crest-derived cells (ENCDC) at the levels where the migrating wave front advances into the hindgut

• at E12.5-E13.5, the delay in hindgut colonization by ENCDCs is greatly enhanced

• in approximately half of the fetuses, ENCDC colonization was not observed in the distal colon even at E15.5

nervous system

abnormal enteric ganglia morphology ( J:135153 )

• the nuclei were found to be abnormally indented, resulting in multilobular nuclei ganglia

cellular

abnormal enteric neural crest cell migration ( J:135153 )

• a slight delay at E11.5 in the migratory behavior of enteric neural crest-derived cells (ENCDC) at the levels where the migrating wave front advances into the hindgut

• at E12.5-E13.5, the delay in hindgut colonization by ENCDCs is greatly enhanced

• in approximately half of the fetuses, ENCDC colonization was not observed in the distal colon even at E15.5