Phenotypes associated with this allele

• Allele Symbol: Parp1^tm1Jmdm
• Allele Name: targeted mutation 1, Josiane Menissier de Murcia
• Allele ID: MGI:1857861
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Parp1^tm1Jmdm/Parp1^tm1Jmdm	involves: 129S2/SvPas	MGI:4429603
hm2	Parp1^tm1Jmdm/Parp1^tm1Jmdm	involves: 129S2/SvPas * C57BL/6	MGI:3720168
cx3	Parp1^tm1Jmdm/Parp1^+ Parp2^tm1Jmdm/Parp2^tm1Jmdm	involves: 129S2/SvPas * C57BL/6	MGI:2663030
cx4	Parp1^tm1Jmdm/Parp1^tm1Jmdm Parp2^tm1Jmdm/Parp2^tm1Jmdm	involves: 129S2/SvPas * C57BL/6	MGI:3844236
cx5	Parp1^tm1Jmdm/Parp1^tm1Jmdm Parp3^tm1.2Ics/Parp3^tm1.2Ics	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:4948946

Genotype
MGI:4429603

hm1

• Allelic Composition: Parp1^tm1Jmdm/Parp1^tm1Jmdm
• Genetic Background: involves: 129S2/SvPas

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

immune system

immune system phenotype ( J:47993 )

N • somatic hypermutation rates in memory B cells are normal

mortality/aging

increased mortality induced by ionizing radiation ( J:170941 )

homeostasis/metabolism

increased mortality induced by ionizing radiation ( J:170941 )

Genotype
MGI:3720168

hm2

• Allelic Composition: Parp1^tm1Jmdm/Parp1^tm1Jmdm
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

increased mortality induced by gamma-irradiation ( J:41742 )

• following 8 Gy of gamma-irradiation, half of 6-8-week-old wild-type mice (5/10) die at 15 days postirradiation (p.i), whereas >50% of homozygotes die at 4 days p.i. (8/13), and all mutant mice are dead by 9 days p.i.

• precocious death is caused by dehydration and/or endotoxicosis secondary to the acute toxicity of radiation on the epithelium of the small intestine

increased susceptibility to induced morbidity/mortality ( J:41742 )

• following i.p. injection of a single dose of the alkylating agent N-methyl-N-nitrosourea (MNU; 75 mg/kg body weight) at 4 weeks of age, all homozygotes (19/19) but only 43% of heterozygotes (9/21) die within a 6-week observation period

• 79% of homozygotes die within the first week postinjection of MNU

prenatal lethality, incomplete penetrance ( J:41742 )

• heterozygous crosses yield 21% of homozygotes instead of the expected 25%

• however, homozygotes obtained are viable and fertile and display no gross abnormalities

• in contrast to Parp1^tm1Zqw homozygotes, neither skin hyperplasia nor obesity is observed in these mice

cellular

abnormal cell cycle checkpoint function ( J:41742 )

• following MNU treatment, MEFs obtained from 13.5-day homozygous embryos show a dose-dependent G2/M arrest, indicating impaired cell cycle progression

elevated level of mitotic sister chromatid exchange ( J:41742 )

• at 32 hrs after s.c. implant of 5-bromodeoxyuridine tablets, 2-month-old homozygotes display a 4- to 5-fold increase in the rate of SCEs in bone marrow cells relative to wild-type mice

• when MNU (80 mg/kg) is injected during the second S phase (9 hrs before sacrifice), the rate of SCEs is increased by >2-fold

• when MNU is applied for 30 hrs during two cell cycles, the rate of SCEs increases by ~3-fold, exceeding 40 SCE/cell in mutant mice

increased apoptosis ( J:41742 )

• after exposure to 2 mM MNU, mutant splenocytes die apoptotically within 2-6 hrs displaying DNA fragmentation, not observed in wild-type splenocytes

• the level of spontaneous apoptosis is also higher in mutant splenocytes relative to wild-type cells

• in addition, mutant splenocytes show rapid DNA damage-induced p53 accumulation, not observed in wild-type cells

abnormal leukocyte migration ( J:117701 )

• after exposure to loud-sound stress, homozygotes fail to show an increased population of leukocytes and emigration of leukocytes in vessels of the spiral ligament, consistent with a relative lack of adhesion protein expression

abnormal DNA repair ( J:41742 )

• homozygotes show a severe DNA repair deficiency following exposure to ionizing radiation during G2, and above all S phase, in bone marrow cells, with both chromatid breaks and chromatid exchanges significantly increased relative to wild-type mice

induced chromosome breakage ( J:41742 )

• when exposed to MNU during the second S phase, homozygotes display a 33- to 36-fold increase in chromosome breakage relative to wild-type mice

• when exposed to gamma-rays, homozygotes display a 3-fold increase in the rate of breakage relative to wild-type mice

homeostasis/metabolism

abnormal DNA repair ( J:41742 )

• homozygotes show a severe DNA repair deficiency following exposure to ionizing radiation during G2, and above all S phase, in bone marrow cells, with both chromatid breaks and chromatid exchanges significantly increased relative to wild-type mice

increased mortality induced by gamma-irradiation ( J:41742 )

• following 8 Gy of gamma-irradiation, half of 6-8-week-old wild-type mice (5/10) die at 15 days postirradiation (p.i), whereas >50% of homozygotes die at 4 days p.i. (8/13), and all mutant mice are dead by 9 days p.i.

• precocious death is caused by dehydration and/or endotoxicosis secondary to the acute toxicity of radiation on the epithelium of the small intestine

growth/size/body

decreased body weight ( J:41742 )

• at 6 weeks, the weight of homozygotes is significantly lower than that of wild-type littermates (23.2 3.1 g vs 19 3 g, respectively)

reproductive system

decreased litter size ( J:41742 )

• homozygotes display a reduction in average litter size (4.5 2.4 pups) relative to wild-type or heterozygous mice (7.4 1.9 pups)

hearing/vestibular/ear

decreased susceptibility to noise-induced hearing loss ( J:117701 )

• however, at 4-5 weeks of age, pre-exposed homozygotes show a positive Preyer's reflex and normal vessel anatomy in the cochlear lateral wall, with no significant differences detected in vessel diameter or in vessel density of the stria vascularis or the spiral ligament relative to wild-type mice

• homozygotes may exhibit decreased noise-induced hearing loss, due to less damage to their cochlear vascular system

immune system

abnormal leukocyte migration ( J:117701 )

• after exposure to loud-sound stress, homozygotes fail to show an increased population of leukocytes and emigration of leukocytes in vessels of the spiral ligament, consistent with a relative lack of adhesion protein expression

abnormal inflammatory response ( J:117701 )

• after exposure to loud-sound stress (i.e. broadband noise at 120 dB SPL for 3 hrs/day for two consecutive days), homozygotes fail to show poly-ADP-ribose production in either the marginal cells or cochlear lateral wall endothelial cells or increased expression of adhesion molecules (ICAM-1 and PECAM) and P-selectin activation in vessels of the spiral ligament

hematopoietic system

abnormal leukocyte migration ( J:117701 )

• after exposure to loud-sound stress, homozygotes fail to show an increased population of leukocytes and emigration of leukocytes in vessels of the spiral ligament, consistent with a relative lack of adhesion protein expression

Genotype
MGI:2663030

cx3

• Allelic Composition: Parp1^tm1Jmdm/Parp1⁺; Parp2^tm1Jmdm/Parp2^tm1Jmdm
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:83371 )

• live mutant mice are generated at a less than expected frequency; only 10 versus expected 28 are generated from intercrosses of double heterozygous mutant mice

• mutant mice exhibit preferential lethality of female embryos at E9.5

• female-specific embryonic lethality is associated with specific X-chromosome instability

embryo

embryonic growth arrest ( J:83371 )

• female mutant embryos undergo a developmental growth arrest at around E9.5

reproductive system

reduced female fertility ( J:83371 )

♀ • all viable mutant female mice display severe hypofertility

♀ • however, no other signs of premature aging are observed

decreased litter size ( J:83371 )

• viable female mutant mice produce an average of 3.5 0.6 pups/litter relative to 7.4 0.4 pups/litter observed in wild-type mice

cellular

aneuploidy ( J:83371 )

• ~40% of metaphases exhibit aneuploidy (1X or 3X) consistent with a severe defect in X-chromosome segregation

• 14% of metaphases contain a derivative of one X chromosome fused to an autosomal chromosome

• no Robertsonian fusion and only one dicentric X chromosome were observed, suggesting absence of telomere shortening

chromosomal instability ( J:83371 )

• metaphase analyses of E8.5 embryonic fibroblasts indicate a specific instability of the X chromosome in female, but not in male, mutant mice

Genotype
MGI:3844236

cx4

• Allelic Composition: Parp1^tm1Jmdm/Parp1^tm1Jmdm; Parp2^tm1Jmdm/Parp2^tm1Jmdm
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

embryonic lethality, complete penetrance ( J:83371 )

• double homozygous mutant embryos die at the onset of gastrulation

• by E10.5, 3 out of 17 double homozygous mutant embryos are largely resorbed

embryo

embryonic growth arrest ( J:83371 )

• double homozygous mutant embryos are growth arrested prior to E8.0

• at E8.0-E8.5, 6 out of 21 double homozygous mutant embryos are severely growth retarded and less developed than wild-type embryos

Genotype
MGI:4948946

cx5

• Allelic Composition: Parp1^tm1Jmdm/Parp1^tm1Jmdm; Parp3^tm1.2Ics/Parp3^tm1.2Ics
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

mortality/aging

increased mortality induced by ionizing radiation ( J:170941 )

• 126 days postirradiation, only 4 of 11 mice survive compared with 7 of 9 Parp1^tm1Jmdm homozygotes

homeostasis/metabolism

increased mortality induced by ionizing radiation ( J:170941 )

• 126 days postirradiation, only 4 of 11 mice survive compared with 7 of 9 Parp1^tm1Jmdm homozygotes