Src<tm1Sor> Targeted Allele Detail MGI Mouse (MGI:1857247)

Src^tm1Sor
Targeted Allele Detail

Nomenclature

Symbol:	Src^tm1Sor
Name:	Rous sarcoma oncogene; targeted mutation 1, Philippe Soriano
MGI ID:	MGI:1857247
Synonyms:	src^-
Gene:	Src Location: Chr2:157244180-157297598 bp, + strand Genetic Position: Chr2, 89.0 cM

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:67040
Parent Cell Line:	AB2.1 (ES Cell)
Strain of Origin:	129S7/SvEvBrd-Hprt1^b-m2

Mutation
description

Allele Type:	Targeted (knock-out)
Mutation:	Insertion
	A neomycin cassette was inserted into the first coding exon. Northern blot analysis confirmed that no wild-type transcript was present in homozygous mice. No autophosphorylation activity corresponding to the encoded protein is detectable in homozygous mice. (J:67040)
Inheritance:	Recessive

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 2 strains available Cell Lines: 0 lines available
Carrying any Src Mutation:	115 strains or lines available

Expression

In Mice Carrying this Mutation:

12 assay results

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	hm1	hm2	cx3	cx4	cx5	cx6
behavior/neurological				√
abnormal nursing				√
		hm1	hm2	cx3	cx4	cx5	cx6
craniofacial			√
abnormal craniofacial bone morphology			√
abnormal head morphology			√
absent incisors			√
abnormal tooth eruption			√
failure of tooth eruption			√
broad head			√
		hm1	hm2	cx3	cx4	cx5	cx6
embryogenesis		√
abnormal decidualization		√
		hm1	hm2	cx3	cx4	cx5	cx6
growth/size			√		√	√	√
decreased body size			√		√	√
decreased body weight			√		√
postnatal growth retardation							√
		hm1	hm2	cx3	cx4	cx5	cx6
hematopoietic system			N				√
hematopoietic system phenotype			N
anemia							√
decreased leukocyte cell number							√
increased macrophage cell number							√
decreased bone marrow cell number							√
abnormal spleen morphology							√
abnormal spleen germinal center morphology							√
abnormal splenic cell ratio							√
thymus hypoplasia							√
		hm1	hm2	cx3	cx4	cx5	cx6
immune system			√				√
increased inflammatory response			√
decreased leukocyte cell number							√
increased macrophage cell number							√
abnormal immune system organ morphology							√
abnormal spleen morphology							√
abnormal spleen germinal center morphology							√
abnormal splenic cell ratio							√
thymus hypoplasia							√
lymph node hypoplasia							√
		hm1	hm2	cx3	cx4	cx5	cx6
lethality/postnatal			√		√
postnatal lethality			√		√
		hm1	hm2	cx3	cx4	cx5	cx6
lethality/prenatal-perinatal						√	√
perinatal lethality							√
neonatal lethality						√
		hm1	hm2	cx3	cx4	cx5	cx6
life span/aging			√			√	√
premature death			√			√	√
		hm1	hm2	cx3	cx4	cx5	cx6
limbs/digits/tail			√				√
abnormal limb morphology			√
abnormal long bone morphology			√
abnormal long bone diaphysis morphology			√				√
increased long bone epiphyseal plate size			√
decreased length of long bones			√
		hm1	hm2	cx3	cx4	cx5	cx6
nervous system			N
nervous system phenotype			N
		hm1	hm2	cx3	cx4	cx5	cx6
pigmentation			√
diluted coat color			√
		hm1	hm2	cx3	cx4	cx5	cx6
reproductive system		√		√
abnormal decidualization		√
female infertility		√
reduced female fertility				√
		hm1	hm2	cx3	cx4	cx5	cx6
respiratory system						√
abnormal breathing						√
		hm1	hm2	cx3	cx4	cx5	cx6
skeleton			√			√	√
abnormal craniofacial bone morphology			√
abnormal long bone morphology			√
abnormal long bone diaphysis morphology			√				√
increased long bone epiphyseal plate size			√
decreased length of long bones			√
abnormal bone structure			√
abnormal bone marrow cavity morphology			√				√
abnormal bone marrow morphology			√
abnormal cancellous bone morphology			√				√
decreased cortical bone thickness			√
osteopetrosis			√			√
decreased bone resorption			√
abnormal skeleton development							√
delayed endochondral bone ossification			√
		hm1	hm2	cx3	cx4	cx5	cx6
skin/coat/nails			√
diluted coat color			√
		hm1	hm2	cx3	cx4	cx5	cx6
vision/eye			√
abnormal anterior eye segment morphology			√
delayed eyelid opening			√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Src^tm1Sor/Src^tm1Sor	B6.129S7-Src^tm1Sor/J
reproductive system abnormal decidualization (J:104318) ovariectomized female homozygotes treated with a low dose of estrogen (E2) and a high dose of progesterone (P4), followed by mechanical stimulation of the left uterine horn, showed little or no detectable decidual responses relative to similarly-treated wild-type and heterozygous females, as determined by uterine histology and uterine weight changes in vitro, endometrial stromal cells (ESCs) from wild-type mice became morphologically decidualized when cultured in the presence of E2+P4 for 5 days, whereas ESCs from female homozygotes remained morphologically unchanged however, prolonged treatment with E2+P4 for 10 days elicited both functional and morphological decidualization even in homozygous mutant ESCs female infertility (J:104318) female homozygotes are severely subfertile or infertile, partly due to impaired decidualization resulting from the loss of maternal function in endometrial stromal cells embryogenesis abnormal decidualization (J:104318) ovariectomized female homozygotes treated with a low dose of estrogen (E2) and a high dose of progesterone (P4), followed by mechanical stimulation of the left uterine horn, showed little or no detectable decidual responses relative to similarly-treated wild-type and heterozygous females, as determined by uterine histology and uterine weight changes in vitro, endometrial stromal cells (ESCs) from wild-type mice became morphologically decidualized when cultured in the presence of E2+P4 for 5 days, whereas ESCs from female homozygotes remained morphologically unchanged however, prolonged treatment with E2+P4 for 10 days elicited both functional and morphological decidualization even in homozygous mutant ESCs
Genotype	Allelic Composition	Genetic Background
hm2	Src^tm1Sor/Src^tm1Sor	either: 129S7/SvEvBrd-Src^tm1Sor or (involves: 129S7/SvEvBrd * C57BL/6J)
lethality/postnatal postnatal lethality (J:67040) at 3 weeks of age, only 19% of the mice are homozygous, suggesting a partial prenatal and/or partial early postnatal lethality life span/aging premature death (J:67040) Background Sensitivity: mice on a mixed background survive longer than mice on the inbred 129S7/SvEvBrd genetic background most animals died at 3-4 weeks of age if weaned; one-third of mice could be maintained past 5 weeks if not weaned and kept on a soft food diet growth/size decreased body size (J:67040) by 10-12 days of age, mice are noticeably smaller than controls decreased body weight (J:67040) mice grow more slowly and weigh about one-third to one-half as much as controls skeleton abnormal craniofacial bone morphology (J:67040) facial bones are thickened by fibrous and osseous tissue proliferation and lack of bone resorbtion smaller airway lumina are present due to abnormal facial bone morphology abnormal long bone morphology (J:67040) abnormal long bone diaphysis morphology (J:67040) short diaphysis of the long bones increased long bone epiphyseal plate size (J:67040) thickened growth plates in the long bones decreased length of long bones (J:67040) long bones are shorter in length abnormal bone structure (J:67040) abnormal bone marrow cavity morphology (J:67040) the bone marrow cavity was filled with little room for hematopoietic elements abnormal bone marrow morphology (J:67040) partial absence of bone marrow abnormal cancellous bone morphology (J:67040) there is a widening and extension of the trabecular bone deep into the distal metaphysis and diaphysis the central trabeculae consist of calcified cartilage decreased cortical bone thickness (J:67040) cortical bone is thinner and disorganized osteopetrosis (J:67040) noted in calvarium, nasal turbinates, facial bones, mandible, tibia and femurs; obvious in long bones at P10 and in the crainial bones at birth delayed endochondral bone ossification (J:67040) persistence of endochondrial primary spongiosa decreased bone resorption (J:67040) bone resorption is minimal to absent pigmentation diluted coat color (J:67040) Background Sensitivity: mice on a mixed genetic background exhibit a lighter coat color unlike mice on an inbred 129S7/SvEvBrd genetic background vision/eye abnormal anterior eye segment morphology (J:67040) at later ages, the eyes are frequently cloudy due to secreted material delayed eyelid opening (J:67040) hematopoietic system hematopoietic system phenotype (J:67040) normal red and white cell parameters are seen normal platelet counts are seen no evidence of hemorrhage or platelet dysfunction is seen; mice are capable of wound healing following tail or toe clipping the liver and spleen are normal in size parafollicular cells of the thyroid are normal Kuppfer cells in the liver are normal in quantity and morphology nervous system nervous system phenotype (J:67040) no microscopic brain lesions are apparent in multiple substructures general brain architecture is normal and axon extension and fasciculation appear normal immune system increased inflammatory response (J:67040) suppurative peridontal inflammation is seen in some animals necrotic debris and acute inflammatory cells are sometimes seen within the lumen of the nasolacrimal duct craniofacial abnormal craniofacial bone morphology (J:67040) facial bones are thickened by fibrous and osseous tissue proliferation and lack of bone resorbtion smaller airway lumina are present due to abnormal facial bone morphology abnormal head morphology (J:67040) mice have a slightly domed head absent incisors (J:67040) incisors are absent at 3 weeks of age incisor teeth are well developed, but fail to erupt through the gum abnormal tooth eruption (J:67040) some molar teeth show partial eruption, but are crowded by osseous growth of the facial bones failure of tooth eruption (J:67040) incisor teeth are well developed, but fail to erupt through the gum broad head (J:67040) mice have a broad face skin/coat/nails diluted coat color (J:67040) Background Sensitivity: mice on a mixed genetic background exhibit a lighter coat color unlike mice on an inbred 129S7/SvEvBrd genetic background limbs/digits/tail abnormal limb morphology (J:67040) enlarged, club-shaped extremities abnormal long bone morphology (J:67040) abnormal long bone diaphysis morphology (J:67040) short diaphysis of the long bones increased long bone epiphyseal plate size (J:67040) thickened growth plates in the long bones decreased length of long bones (J:67040) long bones are shorter in length
Genotype	Allelic Composition	Genetic Background
cx3	Fyn^tm1Sor/Fyn^tm1Sor Src^tm1Sor/Src⁺	involves: 129S7/SvEvBrd
behavior/neurological abnormal nursing (J:20346) difficulty in nursing newborn pups on the occasional cases where females became pregnant reproductive system reduced female fertility (J:20346)
Genotype	Allelic Composition	Genetic Background
cx4	Fyn^tm1Sor/Fyn^tm1Sor Src^tm1Sor/Src^tm1Sor	involves: 129S7/SvEvBrd
lethality/postnatal postnatal lethality (J:20346) only 10% of animals survived to weaning age; normal Mendelian ratios were present at E18.5; animals did not survive past 3 weeks of age growth/size decreased body size (J:20346) animals were described as very small decreased body weight (J:20346) at 3 weeks of age, animals weighed 3-4 grams compared to controls weighing 8 grams
Genotype	Allelic Composition	Genetic Background
cx5	Src^tm1Sor/Src^tm1Sor Yes1^tm1Sor/Yes1^tm1Sor	involves: 129S7/SvEvBrd
lethality/prenatal-perinatal neonatal lethality (J:20346) incomplete penetrance; only 10% of animals survived to weaning age; normal Mendelian ratios were present at E18.5, but many were found dead shortly after birth life span/aging premature death (J:20346) some animals survived past weaning age; one survived to one year of age on a soft food diet growth/size decreased body size (J:20346) embryos at E18.5 were approximately 25% smaller than controls despite normal placenta morphology respiratory system abnormal breathing (J:20346) animals delivered by Cesarean at E18.5 only started to breathe normally after one hour of prodding skeleton osteopetrosis (J:20346) no more severe than in homozygous Src mutant mice
Genotype	Allelic Composition	Genetic Background
cx6	Hck^tm1Hev/Hck^tm1Hev Src^tm1Sor/Src^tm1Sor	involves: 129S7/SvEvBrd * C57BL/6J
lethality/prenatal-perinatal perinatal lethality (J:31647) double homozygotes present at dramatically reduced proportions at 10-14 days of age ratios normal at E18.5 deaths probably occurring perinatally life span/aging premature death (J:31647) approximately 50% die immediately after weaning growth/size postnatal growth retardation (J:31647) little weight gain from 14 to 50 days of age skeleton abnormal long bone diaphysis morphology (J:31647) proximal and distal growth zones are often fused leaving the diaphysis filled with cancellous bone abnormal bone marrow cavity morphology (J:31647) reduced bone marrow cavity abnormal cancellous bone morphology (J:31647) extensive development of cancellous bone reduces bone marrow cavity in long bones, vertebral bodies, sternum accumulations of poorly remodeled osteocartilagenous trabeculae throughout the growth zones of long bones abnormal skeleton development (J:31647) proximal and distal growth zones are often fused leaving the diaphysis filled with cancellous bone normal numbers of osteoclasts found immune system decreased leukocyte cell number (J:31647) mild leucopenia at 2-4 weeks of age which is more severe at E18.5 increased macrophage cell number (J:31647) accumulation of mature macrophage in bones abnormal immune system organ morphology (J:31647) abnormal spleen morphology (J:31647) abnormal spleen germinal center morphology (J:31647) absent or poorly formed germinal centers abnormal splenic cell ratio (J:31647) increased number of colony forming units in spleen greatly increased numbers of immature myeloid cells decreased numbers of lymphoid cells thymus hypoplasia (J:31647) reduced cell number in thymus lymph node hypoplasia (J:31647) reduced number of cells in lymph nodes but structure otherwise normal hematopoietic system anemia (J:31647) mild anemia at 2-4 weeks of age which is more severe at E18.5 decreased leukocyte cell number (J:31647) mild leucopenia at 2-4 weeks of age which is more severe at E18.5 increased macrophage cell number (J:31647) accumulation of mature macrophage in bones decreased bone marrow cell number (J:31647) reduced number of colony forming units in bone marrow abnormal spleen morphology (J:31647) abnormal spleen germinal center morphology (J:31647) absent or poorly formed germinal centers abnormal splenic cell ratio (J:31647) increased number of colony forming units in spleen greatly increased numbers of immature myeloid cells decreased numbers of lymphoid cells thymus hypoplasia (J:31647) reduced cell number in thymus limbs/digits/tail abnormal long bone diaphysis morphology (J:31647) proximal and distal growth zones are often fused leaving the diaphysis filled with cancellous bone

References

Original:	J:67040 Soriano P et al., "Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice." Cell 1991 Feb 22;64(4):693-702
All:	43 reference(s)

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