Phenotypes associated with this allele

• Allele Symbol: Serpine2^tm1Dmn
• Allele Name: targeted mutation 1, Denis Monard
• Allele ID: MGI:2387774
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Serpine2^tm1Dmn/Serpine2^tm1Dmn	B6.129P2-Serpine2^tm1Dmn	MGI:3524779
hm2	Serpine2^tm1Dmn/Serpine2^tm1Dmn	involves: 129P2/OlaHsd * C57BL/6	MGI:3037539
cx3	Serpine2^tm1Dmn/Serpine2^tm1Dmn Tg(Thy1-Serpine2)2Dmn/?	involves: 129P2/OlaHsd * C57BL/6	MGI:3717709

Genotype
MGI:3524779

hm1

• Allelic Composition: Serpine2^tm1Dmn/Serpine2^tm1Dmn
• Genetic Background: B6.129P2-Serpine2^tm1Dmn

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

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:94811 )

• normal level of activity, balance, speed and coordination

abnormal sensory capabilities/reflexes/nociception ( J:94811 )

• mutants need significantly more time to perform a whisker-sensitive task than wild-type

• whisker trimming did not impair the distance crossed in gap-crossing test as it did in wild-type

nervous system

abnormal cerebellum external granule cell layer morphology ( J:121263 )

• while the overall thickness of the external granular layer (EGL) is unchanged, the outer EGL is thickened and the inner EGL is thinned noticeably at P5 and obviously by P10

• cerebellar granular neuron precursor (CGNP) differentiation is delayed

• proliferating CGNPs are restricted to the pial surface whereas in wild-type mice they are evenly spread through out the outer EGL

abnormal cerebellar granule layer morphology ( J:121263 )

• at P10, the thickness of the inner granular layer (IGL) is increased in the anterior-central part of the cerebellum by 67%

• at P10, the medial cerebellum is most affected by volume increase

• in adult mice, the width of the IGL in posterior lobe VIII is increased by 40% and the IGL of lobe VI is 60% thicker

• mice have a 6% increase in IGL volume at P10 and by adulthood the increase reached 12.2%

• volume increase in the anterior, medial and posterior lobes of the cerebellum are 11.3%, 9.3% and 15.4%, respectively, in adults lobe IX protrudes more than in wild-type mice

abnormal astrocyte morphology ( J:121263 )

• Bergmann glial cell fibers have increased thickness, appear irregular and contact the pial surface with larger endfeet in comparison to wild-type

decreased Schwann cell number ( J:121223 )

• following crush damage, Schwann cell proliferation is decreased and apoptosis rates are increased

abnormal sciatic nerve morphology ( J:121223 )

• at 12 days following sciatic nerve crush, axonal regeneration in the sciatic nerve in the triceps surae muscle is delayed

• responsiveness following injury is delayed and mice do not regain full use of their limb until 2 to 4 days later than wild-type mice

delayed peripheral nervous system regeneration ( J:121223 )

• at 12 days following sciatic nerve crush, axonal regeneration in the sciatic nerve in the triceps surae muscle is delayed

• responsiveness following injury is delayed and mice do not regain full use of their limb until 2 to 4 days later than wild-type mice

reduced NMDA receptor mediated synaptic activity in barrel cortex ( J:94811 )

• decreased sensory-evoked potential in the somatosensory cortex

abnormal excitatory postsynaptic currents ( J:94811 )

• strong reduction in excitatory postsynaptic currents at +40 mV compared to wild-type but no difference from wild-type at 60 mV, indicating a deficiency in NMDA receptors

cellular

increased cell proliferation ( J:121263 )

• in vitro, cerebrellar granular neuron precursors (CGNPs) and glial cells a two-fold higher basal proliferative rate and a much stronger proliferative response compared to wild-type cells following Shh treatment

• in vitro, CGNPs show a 28% increase in proliferation

homeostasis/metabolism

abnormal acute phase protein level ( J:121263 )

• fibrin accumulates following peripheral nerve damage

abnormal response to injury ( J:121223 )

• at 12 days following sciatic nerve crush, axonal regeneration in the sciatic nerve in the triceps surae muscle is delayed

• responsiveness following injury is delayed and mice do not regain full use of their limb until 2 to 4 days later than wild-type mice

• following crush damage, Schwann cell proliferation is decreased and apoptosis rates are increased

immune system

abnormal acute phase protein level ( J:121263 )

• fibrin accumulates following peripheral nerve damage

Genotype
MGI:3037539

hm2

• Allelic Composition: Serpine2^tm1Dmn/Serpine2^tm1Dmn
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:40953 )

• homozygotes exhibit an increased susceptibility to kainic acid (KA)-induced seizures: i.p. KA injection (30 mg/kg) was followed by full clonic spasms and seizures in 6 of 10 mutant mice, with onset times ranging between 16 and 72 min (4/10, only forelegs involved); in contrast, none of the littermate controls showed full clonic spasms but displayed only clonic spasms of the forelegs, with onset times ranging from 30 to 59 min (n = 10)

• in vitro, hippocampal slices exhibit an increased polyspiking activity in the CA1 field on 1 Hz of stimulation, as compared with littermate controls

endocrine/exocrine glands

abnormal seminal vesicle morphology ( J:68075 )

♂ • seminal vesicles show progressive morphological defects starting at 4 months of age; however, morphology is normal at 2 months, when infertility is already observed

♂ • at 4 months, seminal vesicles show a decrease in the number and the depth of the folds of the stromal sheath, obstruction, and/or dilatation of the distal part of the gland

abnormal seminal vesicle epithelium morphology ( J:68075 )

♂ • at 10 months, the vesicular epithelium layer shows decreased organization and the stroma is apparently lost

dilated seminal vesicle ( J:68075 )

♂ • at 10 months, seminal vesicles display a massive dilatation (up to a 3-fold in severe cases)

abnormal prostate gland physiology ( J:68075 )

♂ • the coagulating gland fluid shows an excess of unidentified thrombin-like protease activity

♂ • however, no difference is detected in the coagulating gland protein patterns relative to wild-type controls

reproductive system

reproductive system phenotype ( J:68075 )

♂N • histology of adult testes shows normal spermatogenesis: no abnormalities or loss of cells are observed

♂N • epididymal sperm cells appear normal in terms of number, motility and function as assessed in in vitro fertilization assays

abnormal seminal vesicle morphology ( J:68075 )

♂ • seminal vesicles show progressive morphological defects starting at 4 months of age; however, morphology is normal at 2 months, when infertility is already observed

♂ • at 4 months, seminal vesicles show a decrease in the number and the depth of the folds of the stromal sheath, obstruction, and/or dilatation of the distal part of the gland

abnormal seminal vesicle epithelium morphology ( J:68075 )

♂ • at 10 months, the vesicular epithelium layer shows decreased organization and the stroma is apparently lost

dilated seminal vesicle ( J:68075 )

♂ • at 10 months, seminal vesicles display a massive dilatation (up to a 3-fold in severe cases)

abnormal prostate gland physiology ( J:68075 )

♂ • the coagulating gland fluid shows an excess of unidentified thrombin-like protease activity

♂ • however, no difference is detected in the coagulating gland protein patterns relative to wild-type controls

abnormal copulatory plug biosynthesis ( J:68075 )

♂ • vaginal plugs generated by male homozygotes are smaller, soft and fibrous, fail to lodge tightly in the cervical opening, and weigh only about one third the weight of wild-type vaginal plugs

♂ • abnormal vaginal plug formation is primarily is attributed to loss of semenoclotin (a major constituent of the copulatory plug)

♂ • malformed plugs are unable to seal the vagina, leading to a reduction in the number of sperm reaching the uterus after coitus

reduced male fertility ( J:68075 )

♂ • matings with homozygous mutant males result in fewer pregnancies than with wild-type or heterozygous males; only a few litters are obtained and these have a reduced average size

♂ • in contrast, heterozygous and homozygous mutant female mice show no indications of impaired fertility

abnormal seminal vesicle fluid composition ( J:68075 )

♂ • at 2 months, the protein profile of seminal fluid displays loss of many proteins, including semenoclotin, as well as increased proteolytic activity, including a 6.8-fold reduction in thrombin inhibitory activity

♂ • at 4 months, seminal vesicles show a yellowish tint in the secretory fluid

♂ • at 10 months, the secretory fluid has a strong yellow-brownish coloration, unlike the white appearance of wild-type seminal vesicles

nervous system

increased susceptibility to pharmacologically induced seizures ( J:40953 )

• homozygotes exhibit an increased susceptibility to kainic acid (KA)-induced seizures: i.p. KA injection (30 mg/kg) was followed by full clonic spasms and seizures in 6 of 10 mutant mice, with onset times ranging between 16 and 72 min (4/10, only forelegs involved); in contrast, none of the littermate controls showed full clonic spasms but displayed only clonic spasms of the forelegs, with onset times ranging from 30 to 59 min (n = 10)

• in vitro, hippocampal slices exhibit an increased polyspiking activity in the CA1 field on 1 Hz of stimulation, as compared with littermate controls

abnormal excitatory postsynaptic potential ( J:40953 )

• homozygotes show a reduction of the NMDA receptor-mediated component of EPSC in the CA1 field of hippocampal slices: the ratio between the NMDA receptor-mediated and the non-NMDA receptor-mediated components of the synaptic EPSC is diminished

reduced long-term potentiation ( J:40953 )

• homozygotes display a reduction in theta burst-induced long-term potentiation (LTP) in the CA1 field of hippocampal slices

• in contrast to theta burst-induced LTP, no changes are detected in late LTP (L-LTP) induced via a strong tetanization

Genotype
MGI:3717709

cx3

• Allelic Composition: Serpine2^tm1Dmn/Serpine2^tm1Dmn; Tg(Thy1-Serpine2)2Dmn/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

cellular

decreased Schwann cell proliferation ( J:121223 )

• following crush damage, Schwann cell proliferation is decreased

nervous system

abnormal sciatic nerve morphology ( J:121223 )

• at 12 days following sciatic nerve crush, axonal regeneration in the sciatic nerve in the triceps surae muscle is delayed

• responsiveness following injury is delayed and mice do not regain full use of their limb until 2 to 4 days later than wild-type mice

abnormal Schwann cell physiology ( J:121223 )

• following crush damage, Schwann cell proliferation is decreased and apoptosis rates are increased

decreased Schwann cell proliferation ( J:121223 )

• following crush damage, Schwann cell proliferation is decreased

delayed peripheral nervous system regeneration ( J:121223 )

• at 12 days following sciatic nerve crush, axonal regeneration in the sciatic nerve in the triceps surae muscle is delayed

• responsiveness following injury is delayed and mice do not regain full use of their limb until 2 to 4 days later than wild-type mice

homeostasis/metabolism

abnormal response to injury ( J:121223 )

• at 12 days following sciatic nerve crush, axonal regeneration in the sciatic nerve in the triceps surae muscle is delayed

• responsiveness following injury is delayed and mice do not regain full use of their limb until 2 to 4 days later than wild-type mice

• following crush damage, Schwann cell proliferation is decreased and apoptosis rates are increased