Phenotypes associated with this allele

• Allele Symbol: Itgb1^tm1Lscd
• Allele Name: targeted mutation 1, Caroline H Damsky
• Allele ID: MGI:2154540
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Itgb1^tm1Lscd/Itgb1^tm1Lscd	involves: 129X1/SvJ * Black Swiss	MGI:3835203
cn2	Itgb1^tm1Lscd/Itgb1^tm1Ref Tg(PLAT-cre)116Sdu/0	involves: 129S1/Sv * 129X1/SvJ	MGI:3624521
cn3	Itgb1^tm1Lscd/Itgb1^tm1Mll Tg(Nes-cre)1Kln/0	involves: 129X1/SvJ * C57BL/6 * SJL	MGI:3703619
cn4	Itgb1^tm1Lscd/Itgb1^tm1Ref Tg(PLAT-cre)116Sdu/0	Not Specified	MGI:3052537

Genotype
MGI:3835203

hm1

• Allelic Composition: Itgb1^tm1Lscd/Itgb1^tm1Lscd
• Genetic Background: involves: 129X1/SvJ * Black Swiss

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

mortality/aging

embryonic lethality between implantation and somite formation, complete penetrance ( J:28266 )

• lethality occurs between E4.5 and E5.5 due to inner cell mass defects

embryo

abnormal blastocoele morphology ( J:28266 )

• E4.5 embryos have collapsed blastocoeles

abnormal inner cell mass morphology ( J:28266 )

• isolated inner cell masses attach, spread and differentiate very poorly on a fibronectin substrate

inner cell mass degeneration ( J:28266 )

• inner cell mass of cultured blastocytes have highly restricted growth and defective endoderm morphogenesis and migration

• 48 hours of blastocyst culture in serum leads to inner cell masses that are significantly smaller and appear disorganized compared to controls

abnormal trophoblast layer morphology ( J:28266 )

• the trophoblasts of E4.5 embryos fails to extensively invade the maternal decidua

• trophoblast outgrowth from cultured blastocytes is defective when laminin is provided as a substrate

abnormal visceral endoderm morphology ( J:28266 )

• the monolayer of visceral endoderm is not formed in these inner cell masses despite the presence of laminin-positive cell clusters

• only 3 of 17 inner masses demonstrate any morphogenesis of the endoderm under this conditions compared to the 100% morphogenesis that occurs to controls

Genotype
MGI:3624521

cn2

• Allelic Composition: Itgb1^tm1Lscd/Itgb1^tm1Ref; Tg(PLAT-cre)116Sdu/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

nervous system

abnormal neuronal migration ( J:108439 )

• while neuronal processes from segments of the E13.5 proximal midgut penetrate a collagen matrix in the presence of GDNF, the neuron cell bodies or glial cells do not as in the case of wild-type neurons

abnormal enteric neural crest cell morphology ( J:108439 )

• enteric neural crest cells exhibit an abnormal association with neuronal processes

• beginning at E12.5, enteric neural crest cells exhibit increased aggregation and form abnormal clusters that are depend on calcium mechanisms

• in culture, enteric neural crest cells form aggregates instead of forming scattered neuronal networks as do wild-type cells

abnormal enteric neuron morphology ( J:108439 )

• in mutants a severe alteration of the neuronal network rostral to the migratory front in observed

abnormal innervation ( J:108439 )

• bundles of extrinsic neurons innervate the aganglionic segments of the colon

digestive/alimentary system

aganglionic megacolon ( J:108439 )

• majority of newborn mutants have a distended ascending colon and caecum

embryo

abnormal enteric neural crest cell migration ( J:108439 )

• in conditional mutants from E11.5, enteric neural crest cells show a delay in colonization of the gut; difference in distance traveled by cells in mutants and controls increases with time

• neural crest cells from mutants fail to invade the hindgut, leading to an aganglionosis of the descending colon after birth

• however, the number of enteric neural crest cells, differentiation and radial distribution of enteric neural crest cells are normal

• when transplanted into wild-type mice, enteric neural crest cells only migrate 66.5% of the distance that wild-type cells migrate

abnormal enteric neural crest cell morphology ( J:108439 )

• enteric neural crest cells exhibit an abnormal association with neuronal processes

• beginning at E12.5, enteric neural crest cells exhibit increased aggregation and form abnormal clusters that are depend on calcium mechanisms

• in culture, enteric neural crest cells form aggregates instead of forming scattered neuronal networks as do wild-type cells

cellular

abnormal enteric neural crest cell migration ( J:108439 )

• in conditional mutants from E11.5, enteric neural crest cells show a delay in colonization of the gut; difference in distance traveled by cells in mutants and controls increases with time

• neural crest cells from mutants fail to invade the hindgut, leading to an aganglionosis of the descending colon after birth

• however, the number of enteric neural crest cells, differentiation and radial distribution of enteric neural crest cells are normal

• when transplanted into wild-type mice, enteric neural crest cells only migrate 66.5% of the distance that wild-type cells migrate

abnormal neuronal migration ( J:108439 )

• while neuronal processes from segments of the E13.5 proximal midgut penetrate a collagen matrix in the presence of GDNF, the neuron cell bodies or glial cells do not as in the case of wild-type neurons

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:108439

Genotype
MGI:3703619

cn3

• Allelic Composition: Itgb1^tm1Lscd/Itgb1^tm1Mll; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * SJL

mortality/aging

premature death ( J:71122 )

• majority of mutants die prematurely at varying ages during adulthood

neonatal lethality, complete penetrance ( J:71122 )

• a small fraction of mutants die shortly after birth

growth/size/body

postnatal growth retardation ( J:71122 )

• mutants grow more slowly than controls

nervous system

abnormal cortical marginal zone morphology ( J:71122 )

• perturbed cortical marginal zone, where the anchorage of glial endfeet, the remodeling of basement membrane, and the extension of the meningeal cell layer are perturbed

abnormal Cajal-Retzius cell morphology ( J:71122 )

• at E15.5, small gaps in the Cajal-Retzius cell layer are seen; defects get worse with age such that Cajal-Retzius neurons form ectopia within the cortical wall and cell bodies are randomly oriented

abnormal cerebral cortex morphology ( J:71122 )

• cerebral cortical hemispheres are reduced in size and fused at the midline

• the layers of the cerebral cortex have a wavy appearance at E15.5

• cortical neurons invade the marginal zone in some areas and accumulate deep in the cortical wall

• at P2, layers I-IV and sometimes layer V are disrupted

• cell bodies of cortical neurons are less tightly packed within cortical layers

abnormal cerebellum morphology ( J:71122 )

abnormal cerebellum development ( J:71122 )

• a large number of granule cells form ectopia along the fusion lines of adjacent folia and at the cerebellar surface underlying the meninges

abnormal cerebellar foliation ( J:71122 )

• development of cerebellar folia is defective, with mutants exhibiting fusion between adjacent folia

• with age, folia become progressively more distorted with decreased depth of the folia

abnormal cerebellum vermis morphology ( J:71122 )

• the vermis lacks fissures

small cerebellum ( J:71122 )

• reduction in cerebellum size with age

abnormal CNS glial cell morphology ( J:71122 )

• glial fibers in cortical sections between E18.5 and P14 do not develop glial endfeet but terminate at varying positions within the marginal zone close to the meningeal layer

• glial endfeet are absent at the surface of the cerebellum and within the folia, glial fibers occasionally invade the granule cell layer but do not form expanded endfeet at any age

abnormal meninges morphology ( J:71122 )

• the meningeal cell layer does not extend into the developing cerebellar folia and between the cortical hemispheres

• remodeling of the meningeal basement membrane is defective starting at E15.5 and becomes progressively worse such that by P7, extracellular matrix molecules are absent from areas of the brain surface underlying the meninges

vision/eye

abnormal eyelid morphology ( J:71122 )

• mutants exhibit partially closed eyes

behavior/neurological

ataxia ( J:71122 )

Genotype
MGI:3052537

cn4

• Allelic Composition: Itgb1^tm1Lscd/Itgb1^tm1Ref; Tg(PLAT-cre)116Sdu/0
• Genetic Background: Not Specified

mortality/aging

premature death ( J:92060 )

• 90% of mutants die within 1 month of birth

behavior/neurological

abnormal motor coordination/balance ( J:92060 )

• starting a few days after birth mutants develop progressive defects in motor function including an inability to climb on inclined surfaces or cling to a round bar

muscle

muscular atrophy ( J:92060 )

• starting a few days after birth mutants develop progressive muscle atrophy

progressive muscle weakness ( J:92060 )

• starting a few days after birth mutants develop progressive muscle weakness

nervous system

abnormal nervous system morphology ( J:92060 )

• at E13.5 and E14.5 the subcutaneous nerves in mutants were thinner with an abnormal arborization pattern

absent Schwann cell precursors ( J:92060 )

• at E13.5 few or no Schwann cell precursors are seen in the distal part of the developing subcutaneous or muscular innervations however by E16.5 Schwann cell numbers have returned to normal

abnormal innervation pattern to muscle ( J:92060 )

• mutants have decreased intramuscular innervation

abnormal neuromuscular synapse morphology ( J:92060 )

• neuromuscular junctions in the abdominal, soleus, and gastrocnemius muscles and the diaphragm appear immature in mutants at P21

abnormal cranial nerve morphology ( J:92060 )

• at E10.5 transient abnormalities including decreased vagus nerve roots, fusion of nerves IX and X, or absence of nerve IX are seen however by E11.5 cranial nerve patterning has resembles that in controls

abnormal sciatic nerve morphology ( J:92060 )

• at P1 the sciatic nerve is abnormally thin and becomes progressively thinner by P21

• mutants nerves contain myelinated motor axons and large clusters of unsorted axons of varying diameters with few myelinated sensory axons

• at P21 some extracellular matrix free regions are seen in mutants

abnormal myelination ( J:92060 )

• only a few myelinated sensory axons are seen at P21 in the sciatic nerve