Phenotypes associated with this allele

• Allele Symbol: Lifr^tm1Imx
• Allele Name: targeted mutation 1, Immunex
• Allele ID: MGI:1857213
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lifr^tm1Imx/Lifr^tm1Imx	B6;129S7-Lifr^tm1Imx/J	MGI:6093713
hm2	Lifr^tm1Imx/Lifr^tm1Imx	involves: 129P3/J * 129S7/SvEvBrd * C57BL/6	MGI:3768428
ht3	Lifr^tm1Imx/Lifr^+	B6;129S7-Lifr^tm1Imx/J	MGI:6094214

Genotype
MGI:6093713

hm1

• Allelic Composition: Lifr^tm1Imx/Lifr^tm1Imx
• Genetic Background: B6;129S7-Lifr^tm1Imx/J

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

mortality/aging

prenatal lethality, incomplete penetrance ( J:242320 )

• fewer than the expected number (18.7% vs. 25%) of fetuses are seen at E18.5

growth/size/body

decreased fetal size ( J:242320 )

• small size at E18.5

endocrine/exocrine glands

cryptorchism ( J:242320 )

♂ • 100% of fetuses show a ligamentous tethering of the testis to the dorsal aorta impairing testicular descent, indicating cryptorchidism

renal/urinary system

abnormal renal/urinary system morphology ( J:242320 )

• 70% of fetuses show ureter and kidney anomalies at E18.5, with 10% having severe and 60% having milder anomalies

• various abnormalities are seen in fetuses, including mild or severe hydronephrosis, a dilated renal collecting system, blind-ending ureter, hydroureter, microcystically dilated tubules, and ureter ectopia

abnormal kidney morphology ( J:242320 )

• 10% of fetuses exhibit renal dysplasia

decreased renal glomerulus number ( J:242320 )

• reduction of glomerular number per kidney volume and glomerular volume

abnormal kidney development ( J:242320 )

• E15.5 kidney shows a reduction of comma shaped bodies, premature glomeruli, and all glomerular developmental stages per kidney section

hydronephrosis ( J:242320 )

• in a subset of mutants

small kidney ( J:242320 )

• kidney size is reduced at E15.5

renal hypoplasia ( J:242320 )

• in a subset of mutants

decreased nephron number ( J:242320 )

• nephron number is reduced at E15.5

abnormal ureter morphology ( J:242320 )

• reduction of the proximal, medial and distal ureteric lumen at E18.5

• hypertrophy of the distal ureter wall

abnormal ureter smooth muscle morphology ( J:242320 )

• thickness of the ureteric smooth muscle layer and the urothelium are increased

blind ureter ( J:242320 )

• in a subset of mutants

ectopic ureter ( J:242320 )

• in a subset of mutants

hydroureter ( J:242320 )

• 10% of E18.5 fetuses exhibit severe hydroureter

reproductive system

cryptorchism ( J:242320 )

♂ • 100% of fetuses show a ligamentous tethering of the testis to the dorsal aorta impairing testicular descent, indicating cryptorchidism

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CAKUT		DOID:0080205	OMIM:PS610805	J:242320

Genotype
MGI:3768428

hm2

• Allelic Composition: Lifr^tm1Imx/Lifr^tm1Imx
• Genetic Background: involves: 129P3/J * 129S7/SvEvBrd * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:25253 )

• mice born vaginally or by Caesarian section die within hours of birth with no milk in their stomachs even when placed with foster mothers

embryonic lethality before implantation, incomplete penetrance ( J:25253 )

• fewer than expected mice are recovered at E3.5

skeleton

increased osteoclast cell number ( J:25253 )

• the number of osteoclasts is increased 6-fold (0.4+/-0.1 osteoclasts per mm³ compared to 0.3+/-0.2 osteoclasts per mm³ in wild-type mice)

• the number of osteoclast surfaces is increased 7-fold (4.1+/-0.6% compared to 0.6+/-0.3% in wild-type mice)

abnormal long bone morphology ( J:25253 )

• bone density is lost at the proximal and distal ends of the long bones and metacarpi

abnormal metacarpal bone morphology ( J:25253 )

• bone density is lost at the proximal and distal ends of the long bones and metacarpi

decreased bone mineral density ( J:25253 )

• bone density is lost at the proximal and distal ends of the long bones and metacarpi

• bones are osteopenic

decreased bone volume ( J:25253 )

• bone volume is reduced greater than 3-fold (4.8+/-0.6% compared to 13.4+/-0.9% in wild-type mice)

nervous system

abnormal astrocyte morphology ( J:25253 )

• at E17.5 to E18.5, the number of GFAP+ astrocytes in the spine and brainstem is decreased compared to in wild-type mice

abnormal dorsal root ganglion morphology ( J:25253 )

• E20.5 dorsal root ganglia neurons do not survive in culture when exposed to cytokines that rely on LIFR to mediate their signal unlike wild-type cells

embryo

abnormal placenta morphology ( J:25253 )

• placenta contain more blood pooling than in wild-type mice and are edematous with large fluid-filled spaces and a lack of organization into distinct spongio- and labyrinthine trophoblast zones

• at E17.5, placenta contain excess fibrin in association with the blood lacunae and marginated leukocytes can be detected in some of these enlarged maternal blood spaces

• at E17.5, the lacy appearance of the normal labyrinthine placenta is lost

• however, fetal hematopoiesis is normal

homeostasis/metabolism

increased liver glycogen level ( J:25253 )

• at E18.5, fetal livers contain higher stores of glycogen than in wild-type mice

growth/size/body

decreased body size ( J:25253 )

• some mice are smaller at birth

immune system

increased osteoclast cell number ( J:25253 )

• the number of osteoclasts is increased 6-fold (0.4+/-0.1 osteoclasts per mm³ compared to 0.3+/-0.2 osteoclasts per mm³ in wild-type mice)

• the number of osteoclast surfaces is increased 7-fold (4.1+/-0.6% compared to 0.6+/-0.3% in wild-type mice)

hematopoietic system

increased osteoclast cell number ( J:25253 )

• the number of osteoclasts is increased 6-fold (0.4+/-0.1 osteoclasts per mm³ compared to 0.3+/-0.2 osteoclasts per mm³ in wild-type mice)

• the number of osteoclast surfaces is increased 7-fold (4.1+/-0.6% compared to 0.6+/-0.3% in wild-type mice)

limbs/digits/tail

abnormal metacarpal bone morphology ( J:25253 )

• bone density is lost at the proximal and distal ends of the long bones and metacarpi

liver/biliary system

increased liver glycogen level ( J:25253 )

• at E18.5, fetal livers contain higher stores of glycogen than in wild-type mice

Genotype
MGI:6094214

ht3

• Allelic Composition: Lifr^tm1Imx/Lifr⁺
• Genetic Background: B6;129S7-Lifr^tm1Imx/J

endocrine/exocrine glands

cryptorchism ( J:242320 )

♂ • 42.5% of fetuses show a ligamentous tethering of the testis to the dorsal aorta impairing testicular descent, indicating cryptorchidism

renal/urinary system

abnormal ureter morphology ( J:242320 )

• reduction of the proximal, medial and distal ureteric lumen at E18.5, but to a lesser extent than in homozygotes

hydroureter ( J:242320 )

• 5% of E18.5 fetuses exhibit severe hydroureter

reproductive system

cryptorchism ( J:242320 )

♂ • 42.5% of fetuses show a ligamentous tethering of the testis to the dorsal aorta impairing testicular descent, indicating cryptorchidism